WorldWideScience

Sample records for complement pathway deregulation

  1. The lectin pathway of complement

    DEFF Research Database (Denmark)

    Ballegaard, Vibe Cecilie Diederich; Haugaard, Anna Karen; Garred, P

    2014-01-01

    The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), Ficolin-1, -2......-1, -2 and -3 and CL-11 could have similar functions in HIV infection as the ficolins have been shown to play a role in other viral infections, and CL-11 resembles MBL and the ficolins in structure and binding capacity.......The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), Ficolin-1, -2...

  2. Complement pathways and meningococcal disease : diagnostic aspects

    DEFF Research Database (Denmark)

    Sjöholm, A G; Truedsson, L; Jensenius, Jens Christian

    2001-01-01

    Complement is an immunological effector system that bridges innate and acquired immunity in several ways. There is a striking association between susceptibility to meningococcal disease and various forms of complement deficiency (1,2). In defense against bacterial infection, the most important fu...

  3. Novel Evasion Mechanisms of the Classical Complement Pathway.

    Science.gov (United States)

    Garcia, Brandon L; Zwarthoff, Seline A; Rooijakkers, Suzan H M; Geisbrecht, Brian V

    2016-09-15

    Complement is a network of soluble and cell surface-associated proteins that gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of nonself cells by one of three initiating mechanisms known as the classical, lectin, and alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. Although many complement-inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review, we focus on several recent investigations that revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules. Copyright © 2016 by The American Association of Immunologists, Inc.

  4. Lessons learned from mice deficient in lectin complement pathway molecules

    DEFF Research Database (Denmark)

    Genster, Ninette; Takahashi, Minoru; Sekine, Hideharu

    2014-01-01

    in turn activate downstream complement components, ultimately leading to elimination of the pathogen. Mice deficient in the key molecules of lectin pathway of complement have been generated in order to build knowledge of the molecular mechanisms of the lectin pathway in health and disease. Despite......The lectin pathway of the complement system is initiated when the pattern-recognition molecules, mannose-binding lectin (MBL), ficolins or collectin-11, bind to invading pathogens or damaged host cells. This leads to activation of MBL/ficolin/collectin-11 associated serine proteases (MASPs), which...... differences in the genetic arrangements of murine and human orthologues of lectin pathway molecules, the knockout mice have proven to be valuable models to explore the effect of deficiency states in humans. In addition, new insight and unexpected findings on the diverse roles of lectin pathway molecules...

  5. Lectin Complement Pathway Proteins in Healthy Individuals

    DEFF Research Database (Denmark)

    Troldborg, Anne; Hansen, Annette Gudmann; Hansen, Søren W K

    2017-01-01

    , it is pivotal to know the normal. Our aim was to describe the concentrations of the eleven known proteins of the lectin pathway in serum and plasma and to uncover possible gender differences, age and diurnal variations, which must be taken into account for investigations in different cohorts. We examined...... morning to the middle of night. There were gender differences for most proteins, whereas age did not seem to influence concentration. The present study underlines the necessity of considering which material to use, correct matching and a trial design that takes the nature of the protein into account...

  6. Deregulation of the RB pathway in human testicular germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Lukas, Claudia; Sørensen, Claus S

    2003-01-01

    Deregulation of the RB pathway is shared by most human malignancies. Components upstream of the retinoblastoma tumour suppressor (pRB), namely the INK4 family of cyclin-dependent kinase (CDK) inhibitors, the D-type cyclins, their partner kinases CDK4/CDK6, and pRB as their critical substrate...

  7. Activation of the lectin complement pathway on human renal ...

    African Journals Online (AJOL)

    This study aimed to investigate the roles of high glucose and mannose-binding lectin (MBL) on the activation of the lectin complement pathway (LCP) on human renal glomerular endothelial cells (HRGECs) in vitro. Flow cytometry analysis, immunofluorescence staining and Western blot were used to detect the cell surface ...

  8. Functional assay of the alternative complement pathway of rat serum

    International Nuclear Information System (INIS)

    Coonrod, J.D.; Jenkins, S.D.

    1979-01-01

    Two functional assays of the alternative pathway of complement activation in rat serum were developed. In the first assay, conditions were established for titration of alternative pathway activity by use of the 50% hemolytic end-point of rabbit red blood cells (RaRBC) in serum treated with ethyleneglycol-bis-(beta-aminoethyl ether)-N, N'-tetraacetic acid (EGTA). The second assay of alternative pathway activity was based on the opsonization of heat-killed radiolabeled pneumococci of serotype 25 (Pn25). Opsonization of Pn25 was shown to proceed entirely via the alternative pathway in rat serum. There was excellent correlation between the results obtained with the RaRBC lysis test and those obtained with the opsonization test. Because of its technical simplicity, the RaRBC lysis test appeared to be the single most useful test of alternative pathway activity in rat serum. (Auth.)

  9. Deregulation of purine pathway in Bacillus subtilis and its use in riboflavin biosynthesis

    Science.gov (United States)

    2014-01-01

    Background Purine nucleotides are essential metabolites for living organisms because they are involved in many important processes, such as nucleic acid synthesis, energy supply, and biosynthesis of several amino acids and riboflavin. Owing to the pivotal roles of purines in cell physiology, the pool of intracellular purine nucleotides must be maintained under strict control, and hence the de novo purine biosynthetic pathway is tightly regulated by transcription repression and inhibition mechanism. Deregulation of purine pathway is essential for this pathway engineering in Bacillus subtilis. Results Deregulation of purine pathway was attempted to improve purine nucleotides supply, based on a riboflavin producer B. subtilis strain with modification of its rib operon. To eliminate transcription repression, the pur operon repressor PurR and the 5’-UTR of pur operon containing a guanine-sensing riboswitch were disrupted. Quantitative RT-PCR analysis revealed that the relative transcription levels of purine genes were up-regulated about 380 times. Furthermore, site-directed mutagenesis was successfully introduced into PRPP amidotransferase (encoded by purF) to remove feedback inhibition by homologous alignment and analysis. Overexpression of the novel mutant PurF (D293V, K316Q and S400W) significantly increased PRPP amidotransferase activity and triggered a strong refractory effect on purine nucleotides mediated inhibition. Intracellular metabolite target analysis indicated that the purine nucleotides supply in engineered strains was facilitated by a stepwise gene-targeted deregulation. With these genetic manipulations, we managed to enhance the metabolic flow through purine pathway and consequently increased riboflavin production 3-fold (826.52 mg/L) in the purF-VQW mutant strain. Conclusions A sequential optimization strategy was applied to deregulate the rib operon and purine pathway of B. subtilis to create genetic diversities and to improve riboflavin production

  10. Signaling pathway deregulation and molecular alterations across pediatric medulloblastomas.

    Science.gov (United States)

    Lhermitte, B; Blandin, A F; Coca, A; Guerin, E; Durand, A; Entz-Werlé, N

    2018-05-15

    Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs). This stratification moved forward recently to better define these groups and their correlation to outcome. This new stratification into 7 novel subgroups was helpful to lay foundations and complementary data on the understanding regarding molecular pathways and gene mutations underlying medulloblastoma biology. This review was aimed at answering the recent key questions on MB genomics and go further in the relevance of those genes in MB development as well as in their targeted therapies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Malaria parasite evasion of classical complement pathway attack

    DEFF Research Database (Denmark)

    Larsen, Mads Delbo; Ditlev, Sisse; Olmos, Rafael Bayarri

    2017-01-01

    of the protective antibodies that are gradually acquired in response to P. falciparum-IEs. Although this response is dominated by IgG1 and IgG3, complement-mediated attack following activation of the classical pathway does not appear to be a major effector mechanism. We hypothesized that this is related to the knob...... is that the knob-restricted expression of PfEMP1 on the IE surface may serve as a hitherto unappreciated immune evasion mechanism employed by P. falciparum parasites....

  12. AMD and the alternative complement pathway: genetics and functional implications.

    Science.gov (United States)

    Tan, Perciliz L; Bowes Rickman, Catherine; Katsanis, Nicholas

    2016-06-21

    Age-related macular degeneration (AMD) is an ocular neurodegenerative disorder and is the leading cause of legal blindness in Western societies, with a prevalence of up to 8 % over the age of 60, which continues to increase with age. AMD is characterized by the progressive breakdown of the macula (the central region of the retina), resulting in the loss of central vision including visual acuity. While its molecular etiology remains unclear, advances in genetics and genomics have illuminated the genetic architecture of the disease and have generated attractive pathomechanistic hypotheses. Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder.

  13. High-frequency deregulated expression of Wnt signaling pathway members in breast carcinomas.

    Science.gov (United States)

    Khan, Zahid; Arafah, Maha; Shaik, Jilani Purusottapatnam; Mahale, Alka; Alanazi, Mohammad Saud

    2018-01-01

    Breast carcinoma is the most common malignancy and leading cause of cancer-related deaths in women worldwide including Saudi Arabia. Breast cancer in Saudi women develops at a much early age with median age of onset of 49 years compared to 62 years observed in patients from USA. Aberrations in wingless and integration site growth factor (Wnt) signaling pathway have been pathologically implicated in development of breast cancers and hence its role was examined in Saudi patients. We immunohistochemically examined various components of Wnt signaling pathway including β-catenin, tumor suppressor proteins, adenomatous polyposis coli (APC), and Axin, expression of naturally occurring pathway antagonists such as Dickkopf Wnt signaling pathway inhibitor 3 (DKK3), FRP2, and WIF1, as well as Wnt target cyclin D1 and c-Myc to establish if the pathway is constitutively activated in breast cancers arising in Saudi women. Cytoplasmic β-catenin, indicative of activation of the pathway, was observed in 24% of cases. Expression of APC and Axin, which are components of β-catenin destruction complex, was lost in 5% and 10% of tumors, respectively. Additionally, Wnt signaling inhibitors DKK3, FRP2, and Wnt inhibitory factor 1 (WIF1) were not expressed in 8%, 14%, and 5% breast tumors, respectively. Overall, accumulation of cytoplasmic β-catenin and downregulation of other Wnt pathway proteins (APC/Axin/DKK3/FRP2/WIF1) were found in approximately half of the breast cancers (47%) in our cohort. Consistent with this, analysis of Wnt target genes demonstrated moderate-to-strong expression of c-Myc in 58% and cyclin D1 in 50% of breast cancers. Deregulation of Wnt pathway was not associated with age of onset of the disease, tumor grade, and triple-negative status of breast cancers. High level of deregulated expression of Wnt pathway proteins suggests its important role in pathogenesis of breast cancers arising in Saudi women who may benefit from development of therapeutic drugs

  14. The Wnt/β-catenin pathway is deregulated in cemento-ossifying fibromas.

    Science.gov (United States)

    Pereira, Thaís Dos Santos Fontes; Diniz, Marina Gonçalves; França, Josiane Alves; Moreira, Rennan Garcias; Menezes, Grazielle Helena Ferreira de; Sousa, Sílvia Ferreira de; Castro, Wagner Henriques de; Gomes, Carolina Cavaliéri; Gomez, Ricardo Santiago

    2018-02-01

    The molecular pathogenesis of cemento ossifying fibroma (COF) is unclear. The purpose of this study was to investigate mutations in 50 oncogenes and tumor suppressor genes, including APC and CTNNB1, in which mutations in COF have been previously reported. In addition, we assessed the transcriptional levels of the Wnt/β-catenin pathway genes in COF. We used a quantitative polymerase chain reaction array to evaluate the transcriptional levels of 44 Wnt/β-catenin pathway genes in 6 COF samples, in comparison with 6 samples of healthy jaws. By using next-generation sequencing (NGS) in 7 COF samples, we investigated approximately 2800 mutations in 50 genes. The expression assay revealed 12 differentially expressed Wnt/β-catenin pathway genes in COF, including the upregulation of CTNNB1, TCF7, NKD1, and WNT5 A, and downregulation of CTNNBIP1, FRZB, FZD6, RHOU, SFRP4, WNT10 A, WNT3 A, and WNT4, suggesting activation of the Wnt/β-catenin signaling pathway. NGS revealed 5 single nucleotide variants: TP53 (rs1042522), PIK3 CA (rs2230461), MET (rs33917957), KIT (rs3822214), and APC (rs33974176), but none of them was pathogenic. Although NGS detected no oncogenic mutation, deregulation of key Wnt/β-catenin signaling pathway genes appears to be relevant to the molecular pathogenesis of COF. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I.

    Science.gov (United States)

    Brockhoff, Marielle; Rion, Nathalie; Chojnowska, Kathrin; Wiktorowicz, Tatiana; Eickhorst, Christopher; Erne, Beat; Frank, Stephan; Angelini, Corrado; Furling, Denis; Rüegg, Markus A; Sinnreich, Michael; Castets, Perrine

    2017-02-01

    Myotonic dystrophy type I (DM1) is a disabling multisystemic disease that predominantly affects skeletal muscle. It is caused by expanded CTG repeats in the 3'-UTR of the dystrophia myotonica protein kinase (DMPK) gene. RNA hairpins formed by elongated DMPK transcripts sequester RNA-binding proteins, leading to mis-splicing of numerous pre-mRNAs. Here, we have investigated whether DM1-associated muscle pathology is related to deregulation of central metabolic pathways, which may identify potential therapeutic targets for the disease. In a well-characterized mouse model for DM1 (HSALR mice), activation of AMPK signaling in muscle was impaired under starved conditions, while mTORC1 signaling remained active. In parallel, autophagic flux was perturbed in HSALR muscle and in cultured human DM1 myotubes. Pharmacological approaches targeting AMPK/mTORC1 signaling greatly ameliorated muscle function in HSALR mice. AICAR, an AMPK activator, led to a strong reduction of myotonia, which was accompanied by partial correction of misregulated alternative splicing. Rapamycin, an mTORC1 inhibitor, improved muscle relaxation and increased muscle force in HSALR mice without affecting splicing. These findings highlight the involvement of AMPK/mTORC1 deregulation in DM1 muscle pathophysiology and may open potential avenues for the treatment of this disease.

  16. Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.

    Directory of Open Access Journals (Sweden)

    Remco Visser

    Full Text Available Sotos syndrome (SoS is characterized by tall stature, characteristic craniofacial features and mental retardation. It is caused by haploinsufficiency of the NSD1 gene. In this study, our objective was to identify downstream effectors of NSD1 and to map these effectors in signaling pathways associated with growth. Genome-wide expression studies were performed on dermal fibroblasts from SoS patients with a confirmed NSD1 abnormality. To substantiate those results, phosphorylation, siRNA and transfection experiments were performed. A significant association was demonstrated with the Mitogen-Activated Protein Kinase (MAPK pathway. Members of the fibroblast growth factor family such as FGF4 and FGF13 contributed strongly to the differential expression in this pathway. In addition, a diminished activity state of the MAPK/ERK pathway was demonstrated in SoS. The Ras Interacting Protein 1 (RASIP1 was identified to exhibit upregulated expression in SoS. It was shown that RASIP1 dose-dependently potentiated bFGF induced expression of the MAPK responsive SBE reporter providing further support for a link between NSD1 and the MAPK/ERK signaling pathway. Additionally, we demonstrated NSD1 expression in the terminally differentiated hypertrophic chondrocytes of normal human epiphyseal growth plates. In short stature syndromes such as hypochondroplasia and Noonan syndrome, the activation level of the FGF-MAPK/ERK-pathway in epiphyseal growth plates is a determining factor for statural growth. In analogy, we propose that deregulation of the MAPK/ERK pathway in SoS results in altered hypertrophic differentiation of NSD1 expressing chondrocytes and may be a determining factor in statural overgrowth and accelerated skeletal maturation in SoS.

  17. A potent complement factor C3 specific nanobody inhibiting multiple functions in the alternative pathway of human and murine complement.

    Science.gov (United States)

    Jensen, Rasmus K; Pihl, Rasmus; Gadeberg, Trine A F; Jensen, Jan K; Andersen, Kasper R; Thiel, Steffen; Laursen, Nick S; Andersen, Gregers Rom

    2018-03-01

    The complement system is a complex, carefully regulated proteolytic cascade for which suppression of aberrant activation is of increasing clinical relevance and inhibition of the complement alternative pathway is a subject of intense research. Here, we describe the nanobody hC3Nb1 that binds to multiple functional states of C3 with sub-nanomolar affinity. The nanobody causes a complete shutdown of alternative pathway activity in human and murine serum when present in concentrations comparable to C3, and hC3Nb1 is shown to prevent both proconvertase assembly as well as binding of the C3 substrate to C3 convertases. Our crystal structure of the C3b-hC3Nb1 complex and functional experiments demonstrate that proconvertase formation is blocked by steric hindrance between the nanobody and an Asn-linked glycan on complement factor B. In addition, hC3Nb1 is shown to prevent factor H binding to C3b rationalizing its inhibition of factor I activity. Our results identify hC3Nb1 as a versatile, inexpensive, and powerful inhibitor of the alternative pathway in both human and murine in vitro model systems of complement activation. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Perioperative functional activity of the alternative pathway of complement in patients with colonic cancer

    DEFF Research Database (Denmark)

    Baatrup, G; Zimmermann-Nielsen, E; Qvist, N

    1999-01-01

    OBJECTIVE: To investigate the functional capacity of the alternative pathway of complement in patients with cancer of the colon before, during, and after operation. DESIGN: Prospective study. SETTING: One university and two district hospitals, Denmark. SUBJECTS: 28 patients having elective...... or emergency operations for colonic cancer. INTERVENTIONS: Measurements of C3b fixing capacity of the alternative complement pathway in serum before, during, and after operation. MAIN OUTCOME MEASUREMENTS: The functional capacity of the alternative pathway of complement, and changes during operation. RESULTS......: The functional capacity of the alternative pathway in patients with cancer of the colon was above normal (p

  19. SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis.

    Science.gov (United States)

    Ferreira, Viviana P; Fazito Vale, Vladimir; Pangburn, Michael K; Abdeladhim, Maha; Mendes-Sousa, Antonio Ferreira; Coutinho-Abreu, Iliano V; Rasouli, Manoochehr; Brandt, Elizabeth A; Meneses, Claudio; Lima, Kolyvan Ferreira; Nascimento Araújo, Ricardo; Pereira, Marcos Horácio; Kotsyfakis, Michalis; Oliveira, Fabiano; Kamhawi, Shaden; Ribeiro, Jose M C; Gontijo, Nelder F; Collin, Nicolas; Valenzuela, Jesus G

    2016-01-13

    Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases.

  20. SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis

    OpenAIRE

    Viviana P. Ferreira; Vladimir Fazito Vale; Michael K. Pangburn; Maha Abdeladhim; Antonio Ferreira Mendes-Sousa; Iliano V. Coutinho-Abreu; Manoochehr Rasouli; Elizabeth A. Brandt; Claudio Meneses; Kolyvan Ferreira Lima; Ricardo Nascimento Araújo; Marcos Horácio Pereira; Michalis Kotsyfakis; Fabiano Oliveira; Shaden Kamhawi

    2016-01-01

    Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the sa...

  1. Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

    DEFF Research Database (Denmark)

    Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine

    2017-01-01

    The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition...... the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system....... Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part...

  2. Complement pathway biomarkers and age-related macular degeneration

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

  3. A journey through the lectin pathway of complement-MBL and beyond

    DEFF Research Database (Denmark)

    Garred, Peter; Genster, Ninette; Pilely, Katrine

    2016-01-01

    , and Carnevale) embryonic development syndrome originates from rare mutations affecting either collectin-11 or MASP-3, indicating a broader functionality of the complement system than previously anticipated. This review summarizes the characteristics of the molecules in the lectin pathway....

  4. A potent complement factor C3 specific nanobody inhibiting multiple functions in the alternative pathway of human and murine complement

    DEFF Research Database (Denmark)

    Jensen, Rasmus K; Pihl, Rasmus; Gadeberg, Trine A F

    2018-01-01

    The complement system is a complex, carefully regulated proteolytic cascade for which suppression of aberrant activation is of increasing clinical relevance and inhibition of the complement alternative pathway is a subject of intense research. Here, we describe the nanobody hC3Nb1 that binds...... to multiple functional states of C3 with sub-nanomolar affinity. The nanobody causes a complete shutdown of alternative pathway activity in human and murine serum when present in concentrations comparable to C3, and hC3Nb1 is shown to prevent both proconvertase assembly as well as binding of the C3 substrate...... to C3 convertases. Our crystal structure of the C3b-hC3Nb1 complex and functional experiments demonstrate that proconvertase formation is blocked by steric hindrance between the nanobody and an Asn-linked glycan on complement factor B. In addition, hC3Nb1 is shown to prevent factor H binding to C3b...

  5. Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation.

    NARCIS (Netherlands)

    Damman, J.; Kok, J.L.; Snieder, H.; Leuvenink, H.G.; Goor, H. van; Hillebrands, J.L.; Dijk, M.C.R.F. van; Hepkema, B.G.; Reznichenko, A.; Born, J. van den; Borst, M.H. de; Bakker, S.J.; Navis, G.J.; Ploeg, R.J.; Seelen, M.A.

    2012-01-01

    In kidney transplantation, complement activation was found to be induced by donor brain death, renal ischemia-reperfusion injury and allograft rejection. There are three known pathways of complement activation: the classical, lectin and the alternative pathway. The lectin complement pathway can be

  6. Collectin-11/MASP complex formation triggers activation of the lectin complement pathway--the fifth lectin pathway initiation complex

    DEFF Research Database (Denmark)

    Ma, Ying Jie; Skjoedt, Mikkel-Ole; Garred, Peter

    2013-01-01

    Collectins and ficolins are important in the clearance of endogenous and exogenous danger materials. A new human collectin-11 was recently identified in low concentration in serum in complex with mannose-binding lectin (MBL)/ficolin-associated serine proteases. Collectin-11 binds to carbohydrate...... complement complex on C. albicans. Moreover, spiking collectin-11-depleted serum, which did not mediate complement activation, with recombinant collectin-11 restored the complement activation capability. These results define collectin-11 as the fifth recognition molecule in the lectin complement pathway...

  7. Pseudomonas aeruginosa alkaline protease blocks complement activation via the classical and lectin pathways.

    Science.gov (United States)

    Laarman, Alexander J; Bardoel, Bart W; Ruyken, Maartje; Fernie, Job; Milder, Fin J; van Strijp, Jos A G; Rooijakkers, Suzan H M

    2012-01-01

    The complement system rapidly detects and kills Gram-negative bacteria and supports bacterial killing by phagocytes. However, bacterial pathogens exploit several strategies to evade detection by the complement system. The alkaline protease (AprA) of Pseudomonas aeruginosa has been associated with bacterial virulence and is known to interfere with complement-mediated lysis of erythrocytes, but its exact role in bacterial complement escape is unknown. In this study, we analyzed how AprA interferes with complement activation and whether it could block complement-dependent neutrophil functions. We found that AprA potently blocked phagocytosis and killing of Pseudomonas by human neutrophils. Furthermore, AprA inhibited opsonization of bacteria with C3b and the formation of the chemotactic agent C5a. AprA specifically blocked C3b deposition via the classical and lectin pathways, whereas the alternative pathway was not affected. Serum degradation assays revealed that AprA degrades both human C1s and C2. However, repletion assays demonstrated that the mechanism of action for complement inhibition is cleavage of C2. In summary, we showed that P. aeruginosa AprA interferes with classical and lectin pathway-mediated complement activation via cleavage of C2.

  8. Tuning complement activation and pathway through controlled molecular architecture of dextran chains in nanoparticle corona.

    Science.gov (United States)

    Coty, Jean-Baptiste; Eleamen Oliveira, Elquio; Vauthier, Christine

    2017-11-05

    The understanding of complement activation by nanomaterials is a key to a rational design of safe and efficient nanomedicines. This work proposed a systematic study investigating how molecular design of nanoparticle coronas made of dextran impacts on mechanisms that trigger complement activation. The nanoparticles used for this work consisted of dextran-coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly characterized. Their different capacity to trigger complement activation established on the cleavage of the protein C3 was also already described making these nanoparticles good models to investigate the relation between the molecular feature of their corona and the mechanism by which they triggered complement activation. Results of this new study show that complement activation pathways can be selected by distinct architectures formed by dextran chains composing the nanoparticle corona. Assumptions that explain the relation between complement activation mechanisms triggered by the nanoparticles and the nanoparticle corona molecular feature were proposed. These results are of interest to better understand how the design of dextran-coated nanomaterials will impact interactions with the complement system. It can open perspectives with regard to the selection of a preferential complement activation pathway or prevent the nanoparticles to activate the complement system, based on a rational choice of the corona configuration. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Complementary Roles of the Classical and Lectin Complement Pathways in the Defense against Aspergillus fumigatus

    DEFF Research Database (Denmark)

    Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine

    2016-01-01

    Aspergillus fumigatus infections are associated with a high mortality rate for immunocompromised patients. The complement system is considered to be important in protection against this fungus, yet the course of activation is unclear. The aim of this study was to unravel the role of the classical......, lectin, and alternative pathways under both immunocompetent and immunocompromised conditions to provide a relevant dual-perspective on the response against A. fumigatus. Conidia (spores) from a clinical isolate of A. fumigatus were combined with various human serum types (including serum deficient...... complement on A. fumigatus, but required classical and/or lectin pathway for initiation. In normal human serum, this initiation came primarily from the classical pathway. However, with a dysfunctional classical pathway (C1q-deficient serum), lectin pathway activated complement and mediated opsonophagocytosis...

  10. Activation of the lectin pathway of complement in experimental human keratitis with Pseudomonas aeruginosa.

    Science.gov (United States)

    Osthoff, Michael; Brown, Karl D; Kong, David C M; Daniell, Mark; Eisen, Damon P

    2014-01-01

    Pseudomonas aeruginosa (P. aeruginosa) microbial keratitis (MK) is a sight-threatening disease. Previous animal studies have identified an important contribution of the complement system to the clearance of P. aeruginosa infection of the cornea. Mannose-binding lectin (MBL), a pattern recognition receptor of the lectin pathway of complement, has been implicated in the host defense against P. aeruginosa. However, studies addressing the role of the lectin pathway in P. aeruginosa MK are lacking. Hence, we sought to determine the activity of the lectin pathway in human MK caused by P. aeruginosa. Primary human corneal epithelial cells (HCECs) from cadaveric donors were exposed to two different P. aeruginosa strains. Gene expression of interleukin (IL)-6, IL-8, MBL, and other complement proteins was determined by reverse transcription-polymerase chain reaction (RT-PCR) and MBL synthesis by enzyme-linked immunosorbent assay and intracellular flow cytometry. MBL gene expression was not detected in unchallenged HCECs. Exposure of HCECs to P. aeruginosa resulted in rapid induction of the transcriptional expression of MBL, IL-6, and IL-8. In addition, expression of several complement proteins of the classical and lectin pathways, but not the alternative pathway, were upregulated after 5 h of challenge, including MBL-associated serine protease 1. However, MBL protein secretion was not detectable 18 h after challenge with P. aeruginosa. MK due to P. aeruginosa triggers activation of MBL and the lectin pathway of complement. However, the physiologic relevance of this finding is unclear, as corresponding MBL oligomer production was not observed.

  11. An assay for the mannan-binding lectin pathway of complement activation

    DEFF Research Database (Denmark)

    Petersen, Steen Vang; Thiel, S; Jensen, L

    2001-01-01

    activation. Therefore, in a generally applicable complement activation assay specific for the MBL pathway, the activity of the classical pathway must be inhibited. This can be accomplished by exploiting the finding that high ionic strength buffers inhibit the binding of C1q to immune complexes and disrupt...

  12. Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway.

    Science.gov (United States)

    Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter

    2017-01-01

    The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination.

  13. Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

    DEFF Research Database (Denmark)

    Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine

    2017-01-01

    the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system....... Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part...... of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination....

  14. An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement.

    Science.gov (United States)

    Wagemakers, Alex; Coumou, Jeroen; Schuijt, Tim J; Oei, Anneke; Nijhof, Ard M; van 't Veer, Cornelis; van der Poll, Tom; Bins, Adriaan D; Hovius, Joppe W R

    2016-04-01

    We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement pathway through interference with mannose binding lectin (MBL) activity. Since Ixodes ricinus is the predominant vector for Lyme borreliosis in Europe and transmits several complement sensitive B. burgdorferi sensu lato (s.l.) strains, we aimed to identify, describe, and characterize the I. ricinus ortholog of TSLPI. We performed (q)PCRs on I. ricinus salivary gland cDNA to identify a TSLPI ortholog. Next, we generated recombinant (r)TSLPI in a Drosophila expression system and examined inhibition of the MBL complement pathway and complement-mediated killing of B. burgdorferi s.l. in vitro. We identified a TSLPI ortholog in I. ricinus salivary glands with 93% homology at the RNA and 89% at the protein level compared to I. scapularis TSLPI, which was upregulated during tick feeding. In silico analysis revealed that TSLPI appears to be part of a larger family of Ixodes salivary proteins among which I. persulcatus basic tail salivary proteins and I. scapularis TSLPI and Salp14. I. ricinus rTSLPI inhibited the MBL complement pathway and protected B. burgdorferi s.s. and Borrelia garinii from complement-mediated killing. We have identified a TSLPI ortholog, which protects B. burgdorferi s.l. from complement-mediated killing in I. ricinus, the major vector for tick-borne diseases in Europe.

  15. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    International Nuclear Information System (INIS)

    Motoo, Yoshiharu; Shimasaki, Takeo; Ishigaki, Yasuhito; Nakajima, Hideo; Kawakami, Kazuyuki; Minamoto, Toshinari

    2011-01-01

    Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation

  16. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Motoo, Yoshiharu, E-mail: motoo@kanazawa-med.ac.jp [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Shimasaki, Takeo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan); Ishigaki, Yasuhito [Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Nakajima, Hideo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Kawakami, Kazuyuki; Minamoto, Toshinari [Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan)

    2011-01-24

    Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

  17. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Toshinari Minamoto

    2011-01-01

    Full Text Available Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer. We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

  18. Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin

    DEFF Research Database (Denmark)

    Pilely, Katrine; Rosbjerg, Anne; Genster, Ninette

    2016-01-01

    Cholesterol crystals (CC) play an essential role in the formation of atherosclerotic plaques. CC activate the classical and the alternative complement pathways, but the role of the lectin pathway is unknown. We hypothesized that the pattern recognition molecules (PRMs) from the lectin pathway bind...... CC and function as an upstream innate inflammatory signal in the pathophysiology of atherosclerosis. We investigated the binding of the PRMs mannose-binding lectin (MBL), ficolin-1, ficolin-2, and ficolin-3, the associated serine proteases, and complement activation products to CC in vitro using...... recognize CC and provides evidence for an important role for this pathway in the inflammatory response induced by CC in the pathophysiology of atherosclerosis....

  19. Activation of the classical pathway of complement by tobacco glycoprotein (TGP).

    Science.gov (United States)

    Koethe, S M; Nelson, K E; Becker, C G

    1995-07-15

    Tobacco glycoprotein (TGP), a polyphenol-rich glycoprotein isolated from tobacco leaves, activates the classical complement pathway through a mechanism that appears to involve direct interaction with C1q. A binding site on C1q for TGP can be localized by competitive inhibition with DNA to a region located in the junction between the collagen-like and globular regions of the molecule. A protein with activity similar to TGP has also been isolated from cigarette smoke condensate (TGP-S); it shares a binding site on C1q with TGP and has similar functional activity, with the exception that complement activation does not proceed to formation of a C3 cleaving enzyme. The ability of TGP and TGP-S to activate complement can be partially duplicated using polyphenols associated with tobacco leaf and smoke, i.e., chlorogenic acid and rutin. These polyphenols also compete with TGP for a binding site on immobilized C1q, suggesting that the polyphenol portion of TGP is critical for activation of complement. These results provide an additional mechanism for complement activation by cigarette products that, in vivo, could result in a localized complement depletion, generation of biologically active complement cleavage products, and initiation of an inflammatory response.

  20. The Emerging Role of Complement Lectin Pathway in Trypanosomatids: Molecular Bases in Activation, Genetic Deficiencies, Susceptibility to Infection, and Complement System-Based Therapeutics

    Directory of Open Access Journals (Sweden)

    Ingrid Evans-Osses

    2013-01-01

    Full Text Available The innate immune system is evolutionary and ancient and is the pivotal line of the host defense system to protect against invading pathogens and abnormal self-derived components. Cellular and molecular components are involved in recognition and effector mechanisms for a successful innate immune response. The complement lectin pathway (CLP was discovered in 1990. These new components at the complement world are very efficient. Mannan-binding lectin (MBL and ficolin not only recognize many molecular patterns of pathogens rapidly to activate complement but also display several strategies to evade innate immunity. Many studies have shown a relation between the deficit of complement factors and susceptibility to infection. The recently discovered CLP was shown to be important in host defense against protozoan microbes. Although the recognition of pathogen-associated molecular patterns by MBL and Ficolins reveal efficient complement activations, an increase in deficiency of complement factors and diversity of parasite strategies of immune evasion demonstrate the unsuccessful effort to control the infection. In the present paper, we will discuss basic aspects of complement activation, the structure of the lectin pathway components, genetic deficiency of complement factors, and new therapeutic opportunities to target the complement system to control infection.

  1. Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

    Science.gov (United States)

    Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

    2015-07-01

    A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia. © 2015 American Heart Association, Inc.

  2. Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques

    DEFF Research Database (Denmark)

    Fumagalli, Stefano; Perego, Carlo; Zangari, Rosalia

    2017-01-01

    Inflammatory mechanisms may be involved in atherosclerotic plaque rupture. By using a novel histology-based method to quantify plaque instability here, we assess whether lectin pathway (LP) of complement activation, a major inflammation arm, could represent an index of plaque instability. Plaques...

  3. The Lectin Complement Pathway in Patients with Necrotizing Soft Tissue Infection

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Rasmussen, Lars S; Pilely, Katrine

    2016-01-01

    BACKGROUND: Mannose-binding lectin (MBL) and ficolins are pattern recognition molecules (PRMs) that play an important role during infection through activation of the lectin complement pathway. We assessed whether plasma PRM levels were associated with mortality in patients with necrotizing soft t...

  4. Study of the optimal reaction conditions for assay of the mouse alternative complement pathway

    NARCIS (Netherlands)

    Dijk, H. van; Rademaker, P.M.; Klerx, J.P.A.M.; Willers, J.M.M.

    1985-01-01

    The optimal reaction conditions for hemolytic assay of alternative complement pathway activity in mouse serum were investigated. A microtiter system was used, in which a number of 7.5×106 rabbit erythrocytes per test well appeared to be optimal. Rabbit erythrocytes were superior as target cells over

  5. An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement

    NARCIS (Netherlands)

    Wagemakers, Alex; Coumou, Jeroen; Schuijt, Tim J.; Oei, Anneke; Nijhof, Ard M.; van 't Veer, Cornelis; van der Poll, Tom; Bins, Adriaan D.; Hovius, Joppe W. R.

    2016-01-01

    We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement

  6. HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role.

    Science.gov (United States)

    Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G

    2018-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4 + /CD25 + T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

  7. HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

    Science.gov (United States)

    Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G.

    2018-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins. PMID:29515558

  8. Depressed activation of the lectin pathway of complement in hereditary angioedema

    DEFF Research Database (Denmark)

    Varga, L; Széplaki, G; Laki, J

    2008-01-01

    ) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured...... by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0.0001) in patients compared with controls. Depressed LP...

  9. Ficolins and the lectin pathway of complement in patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Hein, Estrid; Nielsen, Louise Aas; Nielsen, Christoffer T

    2015-01-01

    The complement system plays a pathophysiological role in systemic lupus erythematosus (SLE). This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE. EDTA plasma samples from 68 Danish SLE patients and 29 healthy...... Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index] (SDI) (Rho=0.27, P=0.026). The Ficolin-1 concentration was also associated with the occurrence of arterial (P=0.0053) but not venous thrombosis (P=0.42). Finally, deposition of C4, C3 and TCC...

  10. Inhibition of the classical pathway of the complement system by saliva of Amblyomma cajennense (Acari: Ixodidae).

    Science.gov (United States)

    Franco, Paula F; Silva, Naylene C S; Fazito do Vale, Vladimir; Abreu, Jéssica F; Santos, Vânia C; Gontijo, Nelder F; Valenzuela, Jesus G; Pereira, Marcos H; Sant'Anna, Mauricio R V; Gomes, Alessandra P S; Araujo, Ricardo N

    2016-05-01

    Inhibition of the complement system during and after haematophagy is of utmost importance for tick success in feeding and tick development. The role of such inhibition is to minimise damage to the intestinal epithelium as well as avoiding inflammation and opsonisation of salivary molecules at the bite site. Despite its importance, the salivary anti-complement activity has been characterised only in species belonging to the Ixodes ricinus complex which saliva is able to inhibit the alternative and lectin pathways. Little is known about this activity in other species of the Ixodidae family. Thus, the aim of this study was to describe the inhibition of the classical pathway of the complement system by the saliva of Amblyomma cajennense at different stages of the haematophagy. The A. cajennense saliva and salivary gland extract (SGE) were able to inhibit the complement classical pathway through haemolytic assays with higher activity observed when saliva was used. The anti-complement activity is present in the salivary glands of starving females and also in females throughout the whole feeding process, with significant higher activity soon after tick detachment. The SGE activity from both females fed on mice or horses had no significant correlation (p > 0.05) with tick body weight. The pH found in the intestinal lumen of A. cajennense was 8.04 ± 0.08 and haemolytic assays performed at pH 8.0 showed activation of the classical pathway similarly to what occurs at pH 7.4. Consequently, inhibition could be necessary to protect the tick enterocytes. Indeed, the inhibition observed by SGE was higher in pH 8.0 in comparison to pH 7.4 reinforcing the role of saliva in protecting the intestinal cells. Further studies should be carried out in order to identify the inhibitor molecule and characterise its inhibition mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification

    DEFF Research Database (Denmark)

    Harboe, Morten; Garred, Peter; Karlstrøm, Ellen

    2009-01-01

    Complement activation plays an important role in human pathophysiology. The effect of classical pathway activation is largely dependent on alternative pathway (AP) amplification, whereas the role of AP for the down-stream effect of mannan-induced lectin pathway (LP) activation is poorly understood...... that AP amplification is quantitatively responsible for the final effect of initial specific LP activation. TCC generation on the solid phase was distinctly but less inhibited by anti-fD. C2 bypass of the LP pathway could be demonstrated, and AP amplification was also essential during C2 bypass in LP...... as shown by complete inhibition of TCC generation in C2-deficient serum by anti-fD and anti-properdin antibodies. In conclusion, the down-stream effect of LP activation depends strongly on AP amplification in normal human serum and in the C2 bypass pathway....

  12. Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, H; Jensenius, Jens Christian; Christensen, I J

    2004-01-01

    BACKGROUND: Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan-binding lectin (MBL) complement activation pathway may cause increased risk of infection......: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. RESULTS: Serum MBL levels were significantly (P cancer (1384 (400-2188) ng/mL) (median...... in the colon or rectum, and disease stages according to Dukes' classification. No statistical difference (P=0.20) in frequency of MBL deficiency was found between the patients (20%) and the donors (27%). CONCLUSIONS: Overall, the MBL complement activation pathway is significantly increased in patients...

  13. Deregulation of a STAT3-IL8 Signaling Pathway Promotes Human Glioblastoma Cell Proliferation and Invasiveness

    Science.gov (United States)

    de la Iglesia, Núria; Konopka, Genevieve; Lim, Kah Leong; Nutt, Catherine L.; Bromberg, Jacqueline F.; Frank, David A.; Mischel, Paul S.; Louis, David N.; Bonni, Azad

    2009-01-01

    Inactivation of the tumor suppressor PTEN is recognized as a major event in the pathogenesis of the brain tumor glioblastoma. However, the mechanisms by which PTEN loss specifically impacts the malignant behavior of glioblastoma cells including their proliferation and propensity for invasiveness remain poorly understood. Genetic studies suggest that the transcription factor STAT3 harbors a PTEN-regulated tumor suppressive function in mouse astrocytes. Here, we report that STAT3 plays a critical tumor suppressive role in PTEN-deficient human glioblastoma cells. Endogenous STAT3 signaling is specifically inhibited in PTEN-deficient glioblastoma cells. Strikingly, reactivation of STAT3 in PTEN-deficient glioblastoma cells inhibits their proliferation, invasiveness, and ability to spread on myelin. We also identify the chemokine IL8 as a novel target gene of STAT3 in human glioblastoma cells. Activated STAT3 occupies the endogenous IL8 promoter and directly represses IL8 transcription. Consistent with these results, IL8 is upregulated in PTEN-deficient human glioblastoma tumors. Importantly, IL8 repression mediates STAT3-inhibition of glioblastoma cell proliferation, invasiveness, and spreading on myelin. Collectively, our findings uncover a novel link between STAT3 and IL8 whose deregulation plays a key role in the malignant behavior of PTEN-deficient glioblastoma cells. These studies suggest that STAT3 activation or IL8 inhibition may have potential in patient-tailored treatment of PTEN-deficient brain tumors. PMID:18524891

  14. Evidence for the Deregulation of Protein Turnover Pathways in Atm-Deficient Mouse Cerebellum: An Organotypic Study.

    Science.gov (United States)

    Kim, Catherine D; Reed, Ryan E; Juncker, Meredith A; Fang, Zhide; Desai, Shyamal D

    2017-07-01

    Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells. In the current study, we show that, as in A-T cells, ISG15 protein expression is elevated in cerebellums and various other tissues obtained from Atm-compromised mice in an Atm-allele-dependent manner (Atm+/+ Atm+/- Atm-/-). Notably, in cerebellums, the brain part primarily affected in A-T, levels of ISG15 were significantly greater (3-fold higher) than cerebrums obtained from the same set of mice. Moreover, as in A-T cell culture, UV induces aberrant degradation of ubiquitylated proteins and autophagy in Atm-deficient, but not in Atm-proficient, cerebellar brain slices grown in culture. Thus, the ex vivo organotypic A-T mouse brain culture model mimics that of an A-T human cell culture model and could be useful for studying the role of ISG15-dependent proteinopathy in cerebellar neurodegeneration, a hallmark of A-T in humans. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  15. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection

    DEFF Research Database (Denmark)

    Ali, Youssif M; Lynch, Nicholas J; Haleem, Kashif S

    2012-01-01

    The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation...... to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse...... of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci....

  16. Effect of deregulation of Sonic Hedgehog pathway on responses to DNA damage and cancer predisposition

    International Nuclear Information System (INIS)

    Charazac, Aurelie

    2015-01-01

    The Gorlin syndrome is a rare genetic disorder characterized by several developmental abnormalities. Due to mutations in PTCH1, a key player of the sonic hedgehog signaling pathway, clinical manifestations also includes hyper-radiosensitivity and an increased predisposition to the development of basal cell carcinomas. Given the implication of DNA repair system defects in hyper-radiosensitivity pathologies, we decided to study the effect of PTCH1 mutations on the DNA damage response in order to better understand the cellular and molecular mechanisms leading to Gorlin's phenotype.This study demonstrate a global failure of the DNA damage repair systems in Gorlin fibroblasts with respect to controls. It highlights in particular the collapse of the base excision repair pathway (BER) responsible for the repair of oxidative DNA damage. (author) [fr

  17. Activation capacity of the alternative and classic complement pathways in patients operated on for colorectal cancer

    DEFF Research Database (Denmark)

    Zimmermann-Nielsen, Erik; Iversen, Lene H; Svehag, Sven-Erik

    2002-01-01

    surgery. The samples were analyzed with an enzyme-linked immunosorbent assay that measured C3 activation capacity by the alternative and classic complement pathways. Cancer patients were compared according to Dukes stage, type of surgery performed, transfusion of blood, development of infection, venous....... Significant differences in C3 activation capacities were observed between cancer patients that were related to Dukes stage and in patients with and without buffy coat-depleted red cells suspended in saline, adenine, glucose, and mannitol transfusion, infectious events, and deep venous thromboembolism...

  18. Maternal and fetal alternative complement pathway activation in early severe preeclampsia.

    Science.gov (United States)

    Hoffman, M Camille; Rumer, Kristen K; Kramer, Anita; Lynch, Anne M; Winn, Virginia D

    2014-01-01

    We sought to determine whether alternative complement activation fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood in cases of severe preeclampsia (PE) compared with normotensive controls. This was a cross-sectional study of women admitted at ≥24 weeks gestation with or without severe PE. Maternal plasma was collected at the time of enrollment. Umbilical venous cord and intervillous space blood were collected at delivery. Plasma Bb levels were assessed using ELISA. Bb levels were compared between cases and controls. Median Bb levels were higher in the maternal plasma of severe PE subjects (n = 24) than in controls (n = 20), 1.45 ± 1.03 versus 0.65 ± 0.23 μg/mL, P < 0.001. In umbilical venous plasma, Bb levels were higher in severe PE subjects (n = 15) compared with controls (n = 15), 2.48 ± 1.40 versus 1.01 ± 0.57 μg/mL, P = 0.01. Activation fragment Bb is increased in the maternal and umbilical venous blood of cases of severe PE when compared with normotensive controls. These data provide support for alternative complement pathway involvement in the pathogenesis of severe PE and demonstrate that alternative complement activation occurs not only in the maternal but also in the fetal compartment. © 2013 John Wiley & Sons Ltd.

  19. Molluskan Hemocyanins Activate the Classical Pathway of the Human Complement System through Natural Antibodies.

    Science.gov (United States)

    Pizarro-Bauerle, Javier; Maldonado, Ismael; Sosoniuk-Roche, Eduardo; Vallejos, Gerardo; López, Mercedes N; Salazar-Onfray, Flavio; Aguilar-Guzmán, Lorena; Valck, Carolina; Ferreira, Arturo; Becker, María Inés

    2017-01-01

    Molluskan hemocyanins are enormous oxygen-carrier glycoproteins that show remarkable immunostimulatory properties when inoculated in mammals, such as the generation of high levels of antibodies, a strong cellular reaction, and generation of non-specific antitumor immune responses in some types of cancer, particularly for superficial bladder cancer. These proteins have the ability to bias the immune response toward a T h 1 phenotype. However, despite all their current uses with beneficial clinical outcomes, a clear mechanism explaining these properties is not available. Taking into account reports of natural antibodies against the hemocyanin of the gastropod Megathura crenulata [keyhole limpet hemocyanin (KLH)] in humans as well as other vertebrate species, we report here for the first time, the presence, in sera from unimmunized healthy donors, of antibodies recognizing, in addition to KLH, two other hemocyanins from gastropods with documented immunomodulatory capacities: Fisurella latimarginata hemocyanin (FLH) and Concholepas concholepas hemocyanin (CCH). Through an ELISA screening, we found IgM and IgG antibodies reactive with these hemocyanins. When the capacity of these antibodies to bind deglycosylated hemocyanins was studied, no decreased interaction was detected. Moreover, in the case of FLH, deglycosylation increased antibody binding. We evaluated through an in vitro complement deposition assay whether these antibodies activated the classical pathway of the human complement system. The results showed that all three hemocyanins and their deglycosylated counterparts elicited this activation, mediated by C1 binding to immunoglobulins. Thus, this work contributes to the understanding on how the complement system could participate in the immunostimulatory properties of hemocyanins, through natural, complement-activating antibodies reacting with these proteins. Although a role for carbohydrates cannot be completely ruled out, in our experimental setting

  20. A zebrafish model for uremic toxicity: role of the complement pathway.

    Science.gov (United States)

    Berman, Nathaniel; Lectura, Melisa; Thurman, Josh; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Reinecke, James; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

    2013-01-01

    Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p 50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement. Copyright © 2013 S. Karger AG, Basel.

  1. Bioactive lysophospholipids generated by hepatic lipase degradation of lipoproteins lead to complement activation via the classical pathway.

    Science.gov (United States)

    Ma, Wanchao; Paik, David C; Barile, Gaetano R

    2014-09-09

    We determined bioactivity of lysophospholipids generated by degradation of the low-density (LDL), very low-density (VLDL), and high-density (HDL) lipoproteins with hepatic lipase (HL), cholesterol esterase (CE), and lipoprotein-associated phospholipase A2 (Lp-PLA2). The LDL, VLDL, and HDL were treated with HL, CE, and Lp-PLA2 after immobilization on plates, and complement activation studies were performed with diluted human serum. Complement component 3 (C3) fixation, a marker for complement activation, was determined with a monoclonal anti-human C3d antibody. Enzymatic properties of HL and CE were assayed with triglyceride and phosphatidylcholine substrates for triglyceride hydrolase and phospholipase A activities. The ARPE-19 cells were used for viability studies. The HL degradation of human lipoproteins LDL, VLDL, or HDL results in the formation of modified lipoproteins that can activate the complement pathway. Complement activation is dose- and time-dependent upon HL and occurs via the classical pathway. Enzymatic studies suggest that the phospholipase A1 activity of HL generates complement-activating lysophospholipids. C-reactive protein (CRP), known to simultaneously interact with complement C1 and complement factor H (CFH), further enhances HL-induced complement activation. The lysophospholipids, 1-Palmitoyl-sn-glycero-3-phosphocholine and 1-Oleoyl-sn-glycero-3-phosphocholine, can be directly cytotoxic to ARPE-19 cells. The HL degradation of lipoproteins, known to accumulate in the outer retina and in drusen, can lead to the formation of bioactive lysophospholipids that can trigger complement activation and induce RPE cellular dysfunction. Given the known risk associations for age-related macular degeneration (AMD) with HL, CRP, and CFH, this study elucidates a possible damage pathway for age-related macular degeneration (AMD) in genetically predisposed individuals, that HL activity may lead to accumulation of lysophospholipids to initiate complement

  2. Significant Deregulated Pathways in Diabetes Type II Complications Identified through Expression Based Network Biology

    Science.gov (United States)

    Ukil, Sanchaita; Sinha, Meenakshee; Varshney, Lavneesh; Agrawal, Shipra

    Type 2 Diabetes is a complex multifactorial disease, which alters several signaling cascades giving rise to serious complications. It is one of the major risk factors for cardiovascular diseases. The present research work describes an integrated functional network biology approach to identify pathways that get transcriptionally altered and lead to complex complications thereby amplifying the phenotypic effect of the impaired disease state. We have identified two sub-network modules, which could be activated under abnormal circumstances in diabetes. Present work describes key proteins such as P85A and SRC serving as important nodes to mediate alternate signaling routes during diseased condition. P85A has been shown to be an important link between stress responsive MAPK and CVD markers involved in fibrosis. MAPK8 has been shown to interact with P85A and further activate CTGF through VEGF signaling. We have traced a novel and unique route correlating inflammation and fibrosis by considering P85A as a key mediator of signals. The next sub-network module shows SRC as a junction for various signaling processes, which results in interaction between NF-kB and beta catenin to cause cell death. The powerful interaction between these important genes in response to transcriptionally altered lipid metabolism and impaired inflammatory response via SRC causes apoptosis of cells. The crosstalk between inflammation, lipid homeostasis and stress, and their serious effects downstream have been explained in the present analyses.

  3. Deregulation of S-adenosylmethionine biosynthesis and regeneration improves methylation in the E. coli de novo vanillin biosynthesis pathway.

    Science.gov (United States)

    Kunjapur, Aditya M; Hyun, Jason C; Prather, Kristala L J

    2016-04-11

    Vanillin is an industrially valuable molecule that can be produced from simple carbon sources in engineered microorganisms such as Saccharomyces cerevisiae and Escherichia coli. In E. coli, de novo production of vanillin was demonstrated previously as a proof of concept. In this study, a series of data-driven experiments were performed in order to better understand limitations associated with biosynthesis of vanillate, which is the immediate precursor to vanillin. Time-course experiments monitoring production of heterologous metabolites in the E. coli de novo vanillin pathway revealed a bottleneck in conversion of protocatechuate to vanillate. Perturbations in central metabolism intended to increase flux into the heterologous pathway increased average vanillate titers from 132 to 205 mg/L, but protocatechuate remained the dominant heterologous product on a molar basis. SDS-PAGE, in vitro activity measurements, and L-methionine supplementation experiments suggested that the decline in conversion rate was influenced more by limited availability of the co-substrate S-adenosyl-L-methionine (AdoMet or SAM) than by loss of activity of the heterologous O-methyltransferase. The combination of metJ deletion and overexpression of feedback-resistant variants of metA and cysE, which encode enzymes involved in SAM biosynthesis, increased average de novo vanillate titers by an additional 33% (from 205 to 272 mg/L). An orthogonal strategy intended to improve SAM regeneration through overexpression of native mtn and luxS genes resulted in a 25% increase in average de novo vanillate titers (from 205 to 256 mg/L). Vanillate production improved further upon supplementation with methionine (as high as 419 ± 58 mg/L), suggesting potential for additional enhancement by increasing SAM availability. Results from this study demonstrate context dependency of engineered pathways and highlight the limited methylation capacity of E. coli. Unlike in previous efforts to improve SAM or

  4. Marked reduction of AKT1 expression and deregulation of AKT1-associated pathways in peripheral blood mononuclear cells of schizophrenia patients.

    Directory of Open Access Journals (Sweden)

    Nico J M van Beveren

    Full Text Available BACKGROUND: Recent studies have suggested that deregulated AKT1 signaling is associated with schizophrenia. We hypothesized that if this is indeed the case, we should observe both decreased AKT1 expression as well as deregulation of AKT1 regulated pathways in Peripheral Blood Mononuclear Cells (PBMCs of schizophrenia patients. OBJECTIVES: To examine PBMC expression levels of AKT1 in schizophrenia patients versus controls, and to examine whether functional biological processes in which AKT1 plays an important role are deregulated in schizophrenia patients. METHODS/RESULTS: A case-control study, investigating whole-genome PBMC gene expression in male, recent onset (<5 years schizophrenia patients (N = 41 as compared to controls (N = 29. Genes, differentially expressed between patients and controls were identified using ANOVA with Benjamini-Hochberg correction (false discovery rate (FDR = 0.05. Functional aspects of the deregulated set of genes were investigated with the Ingenuity Pathway Analysis (IPA Software Tool. We found significantly decreased PBMC expression of AKT1 (p<0.001, t = -4.25 in the patients. AKT1 expression was decreased in antipsychotic-free or -naive patients (N = 11, in florid psychotic (N = 20 and in remitted (N = 21 patients. A total of 1224 genes were differentially expressed between patients and controls (FDR = 0.05. Functional analysis of the entire deregulated gene set indicated deregulated canonical pathways involved in a large number of cellular processes: immune system, cell adhesion and neuronal guidance, neurotrophins and (neural growth factors, oxidative stress and glucose metabolism, and apoptosis and cell-cycle regulation. Many of these processes are associated with AKT1. CONCLUSIONS: We show significantly decreased PBMC gene expression of AKT1 in male, recent-onset schizophrenia patients. Our observations suggest that decreased PBMC AKT1 expression is a stable trait in recent onset

  5. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    Science.gov (United States)

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  6. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bitencourt, C.S. [Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I. [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-02

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

  7. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    International Nuclear Information System (INIS)

    Bitencourt, C.S.; Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I.

    2012-01-01

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production

  8. Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Zanier, Elisa R; Zangari, Rosalia; Munthe-Fog, Lea

    2014-01-01

    OBJECTIVES: To assess the involvement of ficolin-3, the main initiator of the lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and outcome. METHODS: In this preliminary exploratory study, plasma concentration of ficolin-3 and of ficolin-3-mediated functional LCP activity...... the World Federation of Neurosurgical Societies grading scale; vasospasm, defined as neuro-worsening with angiographic confirmation of vessel narrowing; cerebral ischemia, defined as hypodense lesion on CT scan performed before discharge; and 6-month outcome, assessed using the Glasgow Outcome Scale....... RESULTS: In patients, no changes were detected for ficolin-3 compared with controls. Notably, however, ficolin-3-mediated functional LCP activity was reduced. Low levels of plasma ficolin-3 and ficolin-3-mediated functional LCP activity were related to SAH severity, vasospasm, and cerebral ischemia...

  9. DMPD: Complement-mediated phagocytosis--the role of Syk. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16754322 Complement-mediated phagocytosis--the role of Syk. Tohyama Y, Yamamura H. ...IUBMB Life. 2006 May-Jun;58(5-6):304-8. (.png) (.svg) (.html) (.csml) Show Complement-mediated phagocytosis-...-the role of Syk. PubmedID 16754322 Title Complement-mediated phagocytosis--the role of Syk. Authors Tohyama

  10. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  11. Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia.

    Science.gov (United States)

    Broix, Loïc; Jagline, Hélène; Ivanova, Ekaterina; Schmucker, Stéphane; Drouot, Nathalie; Clayton-Smith, Jill; Pagnamenta, Alistair T; Metcalfe, Kay A; Isidor, Bertrand; Louvier, Ulrike Walther; Poduri, Annapurna; Taylor, Jenny C; Tilly, Peggy; Poirier, Karine; Saillour, Yoann; Lebrun, Nicolas; Stemmelen, Tristan; Rudolf, Gabrielle; Muraca, Giuseppe; Saintpierre, Benjamin; Elmorjani, Adrienne; Moïse, Martin; Weirauch, Nathalie Bednarek; Guerrini, Renzo; Boland, Anne; Olaso, Robert; Masson, Cecile; Tripathy, Ratna; Keays, David; Beldjord, Cherif; Nguyen, Laurent; Godin, Juliette; Kini, Usha; Nischké, Patrick; Deleuze, Jean-François; Bahi-Buisson, Nadia; Sumara, Izabela; Hinckelmann, Maria-Victoria; Chelly, Jamel

    2016-11-01

    Neurodevelopmental disorders with periventricular nodular heterotopia (PNH) are etiologically heterogeneous, and their genetic causes remain in many cases unknown. Here we show that missense mutations in NEDD4L mapping to the HECT domain of the encoded E3 ubiquitin ligase lead to PNH associated with toe syndactyly, cleft palate and neurodevelopmental delay. Cellular and expression data showed sensitivity of PNH-associated mutants to proteasome degradation. Moreover, an in utero electroporation approach showed that PNH-related mutants and excess wild-type NEDD4L affect neurogenesis, neuronal positioning and terminal translocation. Further investigations, including rapamycin-based experiments, found differential deregulation of pathways involved. Excess wild-type NEDD4L leads to disruption of Dab1 and mTORC1 pathways, while PNH-related mutations are associated with deregulation of mTORC1 and AKT activities. Altogether, these data provide insights into the critical role of NEDD4L in the regulation of mTOR pathways and their contributions in cortical development.

  12. Electrical deregulation

    International Nuclear Information System (INIS)

    Simpson, R.

    2001-01-01

    Deregulation in the electricity sector took effect on January 1, 2001 in Alberta. Business consumers discovered that their electricity rates had almost doubled in a one-month period. The government argued that it was the case of short term pain for long term gain. The intent of the deregulation is the lowering of prices through competition. This principle applies when the supply meets the demand, but when the demand exceeds the supply, prices increase. When initial plans were made for the deregulation of the sector, utilities did not invest huge amounts of capital to build new generation plants, as it was not known how they would fare in the deregulated environment. This situation was compounded by the fact that there was an economic boom around the same time in Alberta, adding to the demands made on the existing generation infrastructure (approximately 4 per cent per year over the past decade). At the moment, some resource developers such as Syncrude, Amoco, and Daishowa produce their own electricity and export their excess capacity to the provincial grid for general use. The rules of the deregulated market have been clarified and a number of utilities are planning new generation plants and facilities. TransAlta, EPCOR, and Enmax Corp. have announced plans to expand or build new coal-fired plants. Alberta has an estimated 35 billion tonnes of recoverable coal, and 25 million tonnes of coal were used in 1999 to produce 75 per cent of the electricity required in Alberta. Over the next ten years, 4,000 megawatts of new capacity is planned, representing a 50 per cent increase over current levels. AES Corporation, a Virginia power giant, has also announced plans to build a generator in Alberta

  13. CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

    DEFF Research Database (Denmark)

    Nielsen, C H; Marquart, H V; Prodinger, W M

    2001-01-01

    the alternative pathway. Blockade of the CR2 ligand-binding site with the monoclonal antibody FE8 resulted in 56 +/- 13% and 71 +/- 9% inhibition of the C3-fragment and MAC deposition, respectively, whereas the monoclonal antibody HB135, directed against an irrelevant CR2 epitope, had no effect. Blockade......Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5...... processes on CR2, indicate that MAC formation is a consequence of alternative pathway activation....

  14. Telecommunications Deregulation

    OpenAIRE

    Jerry A. Hausman; William E. Taylor

    2012-01-01

    From Fred Kahn's writings and experiences as a telecommunications regulator and commenter, we draw the following conclusions: prices must be informed by costs; costs are actual incremental costs; costs and prices are an outcome of a Schumpeterian competitive process, not the starting point; excluding incumbents from markets is fundamentally anticompetitive; and a regulatory transition to deregulation entails propensities to micromanage the process to generate preferred outcomes, visible compe...

  15. Down-regulation of complement receptors on the surface of host monocyte even as in vitro complement pathway blocking interferes in dengue infection.

    Directory of Open Access Journals (Sweden)

    Cintia Ferreira Marinho

    Full Text Available In dengue virus (DENV infection, complement system (CS activation appears to have protective and pathogenic effects. In severe dengue fever (DF, the levels of DENV non-structural-1 protein and of the products of complement activation, including C3a, C5a and SC5b-9, are higher before vascular leakage occurs, supporting the hypothesis that complement activation contributes to unfavourable outcomes. The clinical manifestations of DF range from asymptomatic to severe and even fatal. Here, we aimed to characterise CS by their receptors or activation product, in vivo in DF patients and in vitro by DENV-2 stimulation on monocytes. In comparison with healthy controls, DF patients showed lower expression of CR3 (CD11b, CR4 (CD11c and, CD59 on monocytes. The DF patients who were high producers of SC5b-9 were also those that showed more pronounced bleeding or vascular leakage. Those findings encouraged us to investigate the role of CS in vitro, using monocytes isolated from healthy subjects. Prior blocking with CR3 alone (CD11b or CR3 (CD11b/CD18 reduced viral infection, as quantified by the levels of intracellular viral antigen expression and soluble DENV non-structural viral protein. However, we found that CR3 alone (CD11b or CR3 (CD11b/CD18 blocking did not influence major histocompatibility complex presentation neither active caspase-1 on monocytes, thus probably ruling out inflammasome-related mechanisms. Although it did impair the secretion of tumour necrosis factor alpha and interferon alpha. Our data provide strategies of blocking CR3 (CD11b pathways could have implications for the treatment of viral infection by antiviral-related mechanisms.

  16. The alternative complement pathway control protein H binds to immune complexes and serves their detection

    International Nuclear Information System (INIS)

    Nydegger, U.E.; Corvetta, A.; Spaeth, P.J.; Spycher, M.

    1983-01-01

    During solubilization of immune complexes C3b becomes fixed to the immunoglobulin part and serves as a receptor for the alternative complement pathway control protein H. The H-C3b immune complex interaction can be made detectable using 4% polyethyleneglycol to separate free from bound 125 I-H. Tetanus toxoid (Te)/anti-Te complexes kept soluble with fresh serum and containing 125 IU of specific antibody bound 18% of 125 I-H; when fresh serum was chelated with 10 mM EDTA, 125 I-H binding was only 5%. On sucrose density gradients, the H-binding material sedimented in the range of 12 to 30 S. In 36 serum samples from rheumatoid arthritis (RA) patients and in 12 serum samples from patients with systemic lupus erythematosus (SLE), 125 I-H binding was significantly elevated to 9.5 +/- 4.7% (mean +/- 1 SD) and 13.3 +/- 5.6%, respectively, while 125 I-H binding by 36 normal human sera was 4 +/- 2%. RA samples (17/36, 47%) and SLE samples (9/12, 75%) had H-binding values increased by more than 2 SD above the normal mean. The serum samples were also assessed for conglutinin- and C1q-binding activities; a significant correlation between H and C1q binding was observed (P less than 0.001); there was no correlation between H and conglutinin binding. Although binding to immune complexes through its interaction with C3b, H clearly detects a population of complexes other than conglutinin, thus expanding the possibilities of further characterizing pathological complexes

  17. Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Alexandra; Chervona, Yana [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States); Hall, Megan [Department of Epidemiology, Mailman School of Public Health, Columbia University, New York (United States); Kluz, Thomas [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States); Gamble, Mary V., E-mail: mvg7@columbia.edu [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York (United States); Costa, Max, E-mail: Max.Costa@nyumc.org [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States)

    2015-05-01

    biological implications. • Both sexes exhibit deregulation of cardiovascular and endocrine pathways.

  18. Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

    International Nuclear Information System (INIS)

    Muñoz, Alexandra; Chervona, Yana; Hall, Megan; Kluz, Thomas; Gamble, Mary V.; Costa, Max

    2015-01-01

    biological implications. • Both sexes exhibit deregulation of cardiovascular and endocrine pathways

  19. A metalloproteinase karilysin present in the majority of Tannerella forsythia isolates inhibits all pathways of the complement system

    DEFF Research Database (Denmark)

    Jusko, Monika; Potempa, Jan; Karim, Abdulkarim Y

    2012-01-01

    Tannerella forsythia is a poorly studied pathogen despite being one of the main causes of periodontitis, which is an inflammatory disease of the supporting structures of the teeth. We found that despite being recognized by all complement pathways, T. forsythia is resistant to killing by human....... forsythia obtained from patients with periodontitis. Taken together, the newly characterized karilysin appears to be an important virulence factor of T. forsythia and might have several important implications for immune evasion....

  20. Multiple activities of LigB potentiate virulence of Leptospira interrogans: inhibition of alternative and classical pathways of complement.

    Directory of Open Access Journals (Sweden)

    Henry A Choy

    Full Text Available Microbial pathogens acquire the immediate imperative to avoid or counteract the formidable defense of innate immunity as soon as they overcome the initial physical barriers of the host. Many have adopted the strategy of directly disrupting the complement system through the capture of its components, using proteins on the pathogen's surface. In leptospirosis, pathogenic Leptospira spp. are resistant to complement-mediated killing, in contrast to the highly vulnerable non-pathogenic strains. Pathogenic L. interrogans uses LenA/LfhA and LcpA to respectively sequester and commandeer the function of two regulators, factor H and C4BP, which in turn bind C3b or C4b to interrupt the alternative or classical pathways of complement activation. LigB, another surface-proximal protein originally characterized as an adhesin binding multiple host proteins, has other activities suggesting its importance early in infection, including binding extracellular matrix, plasma, and cutaneous repair proteins and inhibiting hemostasis. In this study, we used a recent model of ectopic expression of LigB in the saprophyte, L. biflexa, to test the hypothesis that LigB also interacts with complement proteins C3b and C4b to promote the virulence of L. interrogans. The surface expression of LigB partially rescued the non-pathogen from killing by 5% normal human serum, showing 1.3- to 48-fold greater survival 4 to 6 d following exposure to complement than cultures of the non-expressing parental strain. Recombinant LigB7'-12 comprising the LigB-specific immunoglobulin repeats binds directly to human complement proteins, C3b and C4b, with respective K(ds of 43±26 nM and 69±18 nM. Repeats 9 to 11, previously shown to contain the binding domain for fibronectin and fibrinogen, are also important in LigB-complement interactions, which interfere with the alternative and classical pathways measured by complement-mediated hemolysis of erythrocytes. Thus, LigB is an adaptable interface

  1. Genetic Variation in Complement Component 2 of the Classical Complement Pathway is Associated with Increased Mortality and Infection: A Study of 627 Trauma Patients

    Science.gov (United States)

    Morris, John A.; Francois, Cedric; Olson, Paul K.; Cotton, Bryan A.; Summar, Marshall; Jenkins, Judith M.; Norris, Patrick R.; Moore, Jason H.; Williams, Anna E.; McNew, Brent S.; Canter, Jeffrey A.

    2009-01-01

    Trauma is a disease of inflammation. Complement Component 2 (C2) is a protease involved in activation of complement through the classical pathway and has been implicated in a variety of chronic inflammatory diseases. We hypothesized that genetic variation in C2 (E318D) identifies a high-risk subgroup of trauma patients reflecting increased mortality and infection (Ventilator associated pneumonia: VAP). Consequently, genetic variation in C2 may stratify patient risk and illuminate underlying mechanisms for therapeutic intervention. Methods DNA samples from 702 trauma patients were genotyped for C2 E318D and linked with covariates (age: mean 42.8 years, gender: 74% male, ethnicity: 80% Caucasian, mechanism: 84% blunt, ISS: mean 25.0, admission lactate: mean 3.13 mEq/L) and outcomes: mortality 9.9% and VAP: 18.5%. VAP was defined by quantitative bronchoalveolar lavage (>104). Multivariate regression determined the relationship of genotype and covariates to risk of death and VAP. However, patients with ISS ≥ 45 were excluded from the multivariate analysis, as magnitude of injury overwhelms genetics and covariates in determining outcome. Results 52 patients (8.3%) had the high-risk heterozygous genotype, associated with a significant increase in mortality and VAP. Conclusion In 702 trauma patients, 8.3% had a high-risk genetic variation in C2 associated with increased mortality (OR=2.65) and infection (OR=2.00). This variation: 1) Identifies a previously unknown high risk group for infection and mortality; 2) Can be determined on admission; 3) May provide opportunity for early therapeutic intervention; and 4) Requires validation in a distinct cohort of patients. PMID:19430225

  2. The salivary scavenger and agglutinin (SALSA binds MBL and regulates the lectin pathway of complement in solution and on surfaces

    Directory of Open Access Journals (Sweden)

    Martin eParnov Reichhardt

    2012-07-01

    Full Text Available The scavenger receptor cysteine-rich (SRCR protein SALSA, also known as gp340, salivary agglutinin (SAG and deleted in malignant brain tumor 1 (DMBT1, is a 340 kDa glycoprotein expressed on mucosal surfaces and secreted into several body fluids. SALSA binds to a broad variety of microbes and endogenous ligands, such as complement factor C1q, surfactant proteins D and A (SP-D and SP-A and IgA. Our search for novel ligands of SALSA by direct protein-interaction studies led to the identification of mannan binding lectin (MBL as a new binding partner. We observed that surface-associated SALSA activates complement via binding of MBL. On the other hand, soluble SALSA was found to inhibit C. albicans-induced complement activation. Thus, SALSA has a dual complement regulatory function. It activates the lectin pathway when bound to a surface and inhibits it when free in the fluid-phase. These activities are mediated via a direct interaction with MBL.

  3. CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

    DEFF Research Database (Denmark)

    Nielsen, C H; Marquart, H V; Prodinger, W M

    2001-01-01

    of the CR1 binding site with the monoclonal antibody 3D9 also resulted in a minor reduction in MAC deposition, while FE8 and 3D9, in combination, markedly reduced deposition of both C3 fragments (91 +/- 5%) and C9 (95 +/- 3%). The kinetics of C3-fragment and MAC deposition, as well as the dependence of both......Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5...... convertase and consequent formation of membrane attack complexes (MAC). Deposition of C3 fragments and MAC was assessed on human peripheral B lymphocytes in the presence of 30% autologous serum containing 4.4 mM MgCl2/20 mM EGTA, which abrogates the classical pathway of complement without affecting...

  4. Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway

    DEFF Research Database (Denmark)

    Ma, Ying Jie; Hein, Estrid; Munthe-Fog, Lea

    2015-01-01

    and may recognize certain bacteria and fungi, leading to opsonophagocytosis. However, based on its structural and functional similarities with soluble collectins, we hypothesized the existence of a fluid-phase analog of CL-12 released from cells, which may function as a soluble pattern-recognition...... of the terminal complement complex. These results demonstrate the existence of CL-12 in a soluble form and indicate a novel mechanism by which the alternative pathway of complement may be triggered directly by a soluble pattern-recognition molecule....... nonreducing conditions it presented multimeric assembly forms. Immunoprecipitation and Western blot analysis of human umbilical cord plasma enabled identification of a natural soluble form of CL-12 having an electrophoretic mobility pattern close to that of shed soluble recombinant CL-12. Soluble CL-12 could...

  5. Novel assays to assess the functional capacity of the classical, the alternative and the lectin pathways of the complement system

    DEFF Research Database (Denmark)

    Palarasah, Y; Nielsen, C; Sprogøe, U

    2011-01-01

    is therefore of great importance. In this study, we present novel improved enzyme-linked immunosorbent assays for the functional assessment of the three individual pathways of the complement system. The method is applicable at high serum concentrations and we demonstrate that it minimizes both false negative...... as well as false positive results. In particular, for the functional mannose-binding lectin activity it represents an improvement on the existing assays. In this respect, the present assays represent novel improved diagnostic protocols for patients with suspected immunodeficiencies related...

  6. Human T-Cell Leukemia Virus Type 1 Tax-Deregulated Autophagy Pathway and c-FLIP Expression Contribute to Resistance against Death Receptor-Mediated Apoptosis

    Science.gov (United States)

    Wang, Weimin; Zhou, Jiansuo; Shi, Juan; Zhang, Yaxi; Liu, Shilian

    2014-01-01

    ABSTRACT The human T-cell leukemia virus type 1 (HTLV-1) Tax protein is considered to play a central role in the process that leads to adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 Tax-expressing cells show resistance to apoptosis induced by Fas ligand (FasL) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). The regulation of Tax on the autophagy pathway in HeLa cells and peripheral T cells was recently reported, but the function and underlying molecular mechanism of the Tax-regulated autophagy are not yet well defined. Here, we report that HTLV-1 Tax deregulates the autophagy pathway, which plays a protective role during the death receptor (DR)-mediated apoptosis of human U251 astroglioma cells. The cellular FLICE-inhibitory protein (c-FLIP), which is upregulated by Tax, also contributes to the resistance against DR-mediated apoptosis. Both Tax-induced autophagy and Tax-induced c-FLIP expression require Tax-induced activation of IκB kinases (IKK). Furthermore, Tax-induced c-FLIP expression is regulated through the Tax-IKK-NF-κB signaling pathway, whereas Tax-triggered autophagy depends on the activation of IKK but not the activation of NF-κB. In addition, DR-mediated apoptosis is correlated with the degradation of Tax, which can be facilitated by the inhibitors of autophagy. IMPORTANCE Our study reveals that Tax-deregulated autophagy is a protective mechanism for DR-mediated apoptosis. The molecular mechanism of Tax-induced autophagy is also illuminated, which is different from Tax-increased c-FLIP. Tax can be degraded via manipulation of autophagy and TRAIL-induced apoptosis. These results outline a complex regulatory network between and among apoptosis, autophagy, and Tax and also present evidence that autophagy represents a new possible target for therapeutic intervention for the HTVL-1 related diseases. PMID:24352466

  7. Structural Basis for Eculizumab-Mediated Inhibition of the Complement Terminal Pathway

    DEFF Research Database (Denmark)

    Schatz-Jakobsen, Janus Asbjørn; zhang, yuchun; Johnson, Krista

    2016-01-01

    the structural observations of the interaction are supported by the reduced ability of a subset of these mutated antibodies to inhibit MAC formation as tested in a hemolysis assay. Our results suggest that eculizumab functions by sterically preventing C5 from binding to convertases and explain the exquisite......Eculizumab is a humanized monoclonal antibody approved for treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uraemic syndrome. Eculizumab binds complement component C5 and prevents its cleavage by C5 convertases, inhibiting release of both...

  8. Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53

    Directory of Open Access Journals (Sweden)

    Arindam Datta

    2016-06-01

    Full Text Available Mutation in TP53 is a common genetic alteration in human cancers. Certain tumor associated p53 missense mutants acquire gain-of-function (GOF properties and confer oncogenic phenotypes including enhanced chemoresistance. The colorectal cancers (CRC harboring mutant p53 are generally aggressive in nature and difficult to treat. To identify a potential gene expression signature of GOF mutant p53-driven acquired chemoresistance in CRC, we performed transcriptome profiling of floxuridine (FUdR treated SW480 cells expressing mutant p53R273H (GEO#: GSE77533. We obtained several genes differentially regulated between FUdR treated and untreated cells. Further, functional characterization and pathway analysis revealed significant enrichment of crucial biological processes and pathways upon FUdR treatment in SW480 cells. Our data suggest that in response to chemotherapeutics treatment, cancer cells with GOF mutant p53 can modulate key cellular pathways to withstand the cytotoxic effect of the drugs. The genes and pathways identified in the present study can be further validated and targeted for better chemotherapy response in colorectal cancer patients harboring mutant p53.

  9. Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, H; Jensenius, Jens Christian; Christensen, I J

    2004-01-01

    in certain patient groups. It is hypothesized that a deficient MBL pathway might be more frequent among patients with CRC than in healthy individuals. The MBL pathway was therefore evaluated in serum obtained preoperatively from 193 patients with primary CRC and in serum from 150 healthy volunteers. METHODS......: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. RESULTS: Serum MBL levels were significantly (P ..., inter-quartile range) compared with levels in healthy blood donors (924 (230-1476) ng/mL). Similarly, the MBL/MASP activity was significantly (P age, gender, tumour location...

  10. Control of the classical and the MBL pathway of complement activation

    DEFF Research Database (Denmark)

    Petersen, Steen Vang; Thiel, S; Jensen, L

    2000-01-01

    and the influence of high ionic strength on the complexes indicate that the activation and control of the MBL pathway differ from that of the classical pathway. MBL deficiency is linked to various clinical manifestations such as recurrent infections, severe diarrhoea, and recurrent miscarriage. On the other hand...... incubation at 37 degrees C in physiological buffer, the associated inhibitors as well as MASP-1, MASP-2, and MAp19 dissociated from MBL, whereas only little dissociation of the complex occurred in buffer with high ionic strength (1 M NaCl). The difference in sensitivity to various inhibitors...

  11. Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway.

    Science.gov (United States)

    Chen, L; Yue, J; Han, X; Li, J; Hu, Y

    2016-02-01

    Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

  12. Regulation of C3 Activation by the Alternative Complement Pathway in the Mouse Retina.

    Directory of Open Access Journals (Sweden)

    Jennifer A E Williams

    Full Text Available The purpose of this study was to examine the retinas of mice carrying hemizygous and null double deletions of Cfb-/- and Cfh-/-, and to compare these with the single knockouts of Cfb, Cfh and Cfd. Retinas were isolated from wild type (WT, Cfb-/-/Cfh-/-, Cfb-/-/Cfh+/-, Cfh-/-/Cfb+/-, Cfb-/-, Cfh-/- Cfd-/-, and Cfd+/- mice. Complement proteins were evaluated by western blotting, ELISA and immunocytochemistry, and retinal morphology was assessed using toluidine blue stained semi-thin sections. WT mice showed staining for C3 and its breakdown products in the retinal vasculature and the basal surface of the retinal pigment epithelium (RPE. Cfb-/- mice exhibited a similar C3 staining pattern to WT in the retinal vessels but a decrease in C3 and its breakdown products at the basal surface of the RPE. Deletion of both Cfb and Cfh restored C3 to levels similar to those observed in WT mice, however this reversal of phenotype was not observed in Cfh-/-/Cfb+/- or Cfb-/-/Cfh+/- mice. Loss of CFD caused an increase in C3 and a decrease in C3 breakdown products along the basal surface of the RPE. Overall the retinal morphology and retinal vasculature did not appear different across the various genotypes. We observed that C3 accumulates at the basal RPE in Cfb-/-, Cfb-/-/Cfh-/-, Cfb-/-/Cfh+/-, Cfd-/- and WT mice, but is absent in Cfh-/- and Cfh-/-/Cfb+/- mice, consistent with its consumption in the serum of mice lacking CFH when CFB is present. C3 breakdown products along the surface of the RPE were either decreased or absent when CFB, CFH or CFD was deleted or partially deleted.

  13. Modulation of post-stroke degenerative and regenerative processes and subacute protection by site-targeted inhibition of the alternative pathway of complement.

    Science.gov (United States)

    Alawieh, Ali; Elvington, Andrew; Zhu, Hong; Yu, Jin; Kindy, Mark S; Atkinson, Carl; Tomlinson, Stephen

    2015-12-30

    Complement promotes neuroinflammation and injury in models of stroke. However, complement is also being increasingly implicated in repair and regeneration after central nervous system (CNS) injury, and some complement deficiencies have been shown to provide acute, but not subacute, protection after murine stroke. Here, we investigate the dual role of complement in injury and repair after cerebral ischemia and reperfusion. We used complement-deficient mice and different complement inhibitors in a model of transient middle cerebral artery occlusion to investigate complement-dependent cellular and molecular changes that occur through the subacute phase after stroke. C3 deficiency and site-targeted complement inhibition with either CR2-Crry (inhibits all pathways) or CR2-fH (inhibits alternative pathway) significantly reduced infarct size, reduced apoptotic cell death, and improved neurological deficit score in the acute phase after stroke. However, only in CR2-fH-treated mice was there sustained protection with no evolution of injury in the subacute phase. Whereas both inhibitors significantly reduced microglia/macrophage activation and astrogliosis in the subacute phase, only CR2-fH improved neurological deficit and locomotor function, maintained neurogenesis markers, enhanced neuronal migration, and increased VEGF expression. These findings in CR2-fH-treated mice correlated with improved performance in spatial learning and passive avoidance tasks. The complement anaphylatoxins have been implicated in repair and regenerative mechanisms after CNS injury, and in this context CR2-fH significantly reduced, but did not eliminate the generation of C5a within the brain, unlike CR2-Crry that completely blocked C5a generation. Gene expression profiling revealed that CR2-fH treatment downregulated genes associated with apoptosis, TGFβ signaling, and neutrophil activation, and decreased neutrophil infiltration was confirmed by immunohistochemistry. CR2-fH upregulated genes for

  14. The Scl1 protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H, and inhibits the alternative pathway of complement.

    Science.gov (United States)

    Caswell, Clayton C; Han, Runlin; Hovis, Kelley M; Ciborowski, Pawel; Keene, Douglas R; Marconi, Richard T; Lukomski, Slawomir

    2008-02-01

    Non-specific activation of the complement system is regulated by the plasma glycoprotein factor H (FH). Bacteria can avoid complement-mediated opsonization and phagocytosis through acquiring FH to the cell surface. Here, we characterize an interaction between the streptococcal collagen-like protein Scl1.6 of M6-type group A Streptococcus (GAS) and FH. Using affinity chromatography with immobilized recombinant Scl1.6 protein, we co-eluted human plasma proteins with molecular weight of 155 kDa, 43 kDa and 38 kDa. Mass spectrometry identified the 155 kDa band as FH and two other bands as isoforms of the FH-related protein-1. The identities of all three bands were confirmed by Western immunoblotting with specific antibodies. Structure-function relation studies determined that the globular domain of the Scl1.6 variant specifically binds FH while fused to collagenous tails of various lengths. This binding is not restricted to Scl1.6 as the phylogenetically linked Scl1.55 variant also binds FH. Functional analyses demonstrated the cofactor activity of the rScl1.6-bound FH for factor I-mediated cleavage of C3b. Finally, purified FH bound to the Scl1.6 protein present in the cell wall material obtained from M6-type GAS. In conclusion, we have identified a functional interaction between Scl1 and plasma FH, which may contribute to GAS evasion of complement-mediated opsonization and phagocytosis.

  15. Costs of electricity deregulation

    International Nuclear Information System (INIS)

    Woo, C.K.; King, M.

    2006-01-01

    The last decade has witnessed efforts throughout the world to deregulate the electricity industry, with varied results. While there have been a few qualified success stories, many challenges of deregulation have come to light. These challenges can lead to negative, even disastrous, outcomes. Based on a comprehensive literature review, this paper catalogues problems experienced in various deregulation efforts, and considers the application of the lessons learned from this history to Israel, which is considering deregulation. Failings of deregulation are found to center around the following problems: high set-up cost; complicated market design; inevitable spot price volatility; market power abuse; inefficient investment; difficulty in reducing generation cost; dysfunctional input markets; stranded cost; unequal distribution of benefits. We find that many of these problems are exacerbated by the particular circumstances faced by Israel, and advise any country or region considering deregulation to carefully consider these obstacles to success. (author)

  16. Genetically engineered fusion of MAP-1 and factor H domains 1-5 generates a potent dual upstream inhibitor of both the lectin and alternative complement pathways

    DEFF Research Database (Denmark)

    Nordmaj, Mie Anemone; Munthe-Fog, Lea; Hein, Estrid

    2015-01-01

    Inhibition of the complement cascade has emerged as an option for treatment of a range of diseases. Mannose-binding lectin/ficolin/collectin-associated protein (MAP-1) is a pattern recognition molecule (PRM)-associated inhibitor of the lectin pathway. The central regulator of the alternative......:4 in a solid-phase functional assay, only the first 5 N-terminal domains of complement FH fused to the C-terminal part of full-length MAP-1 chimeric construct were able to combine inhibition of lectin and AP activation with an half maximal inhibitory concentration of ∼ 100 and 20 nM, respectively. No effect...

  17. Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice

    Directory of Open Access Journals (Sweden)

    Holers V Michael

    2007-05-01

    Full Text Available Abstract Background The posttraumatic response to traumatic brain injury (TBI is characterized, in part, by activation of the innate immune response, including the complement system. We have recently shown that mice devoid of a functional alternative pathway of complement activation (factor B-/- mice are protected from complement-mediated neuroinflammation and neuropathology after TBI. In the present study, we extrapolated this knowledge from studies in genetically engineered mice to a pharmacological approach using a monoclonal anti-factor B antibody. This neutralizing antibody represents a specific and potent inhibitor of the alternative complement pathway in mice. Methods A focal trauma was applied to the left hemisphere of C57BL/6 mice (n = 89 using a standardized electric weight-drop model. Animals were randomly assigned to two treatment groups: (1 Systemic injection of 1 mg monoclonal anti-factor B antibody (mAb 1379 in 400 μl phosphate-buffered saline (PBS at 1 hour and 24 hours after trauma; (2 Systemic injection of vehicle only (400 μl PBS, as placebo control, at identical time-points after trauma. Sham-operated and untreated mice served as additional negative controls. Evaluation of neurological scores and analysis of brain tissue specimens and serum samples was performed at defined time-points for up to 1 week. Complement activation in serum was assessed by zymosan assay and by murine C5a ELISA. Brain samples were analyzed by immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL histochemistry, and real-time RT-PCR. Results The mAb 1379 leads to a significant inhibition of alternative pathway complement activity and to significantly attenuated C5a levels in serum, as compared to head-injured placebo-treated control mice. TBI induced histomorphological signs of neuroinflammation and neuronal apoptosis in the injured brain hemisphere of placebo-treated control mice for up to 7 days. In contrast, the

  18. Activation and binding of opsonic fragments of C3 on encapsulated Cryptococcus neoformans by using an alternative complement pathway reconstituted from six isolated proteins.

    Science.gov (United States)

    Kozel, T R; Wilson, M A; Pfrommer, G S; Schlageter, A M

    1989-07-01

    Encapsulated Cryptococcus neoformans yeast cells are potent activators of the complement system. We examined the interaction of the yeast cells with an alternative complement pathway reconstituted from isolated factor D, factor B, factor H, factor I, C3, and properdin. Incubation of encapsulated cryptococci with the reconstituted pathway led to activation and binding of C3 fragments to the yeast cells that was quantitatively and qualitatively identical to that observed with normal human serum. Incubation with either normal serum or a mixture of isolated proteins led to binding of 4 x 10(7) to 5 x 10(7) C3 molecules to the yeast cells. The kinetics for activation and binding of C3 were identical, with maximum binding observed after a 20-min incubation. Immunoglobulin G was not needed for optimal activation kinetics. C3 fragments eluted from the yeast cells by treatment with hydroxylamine and subsequent analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated the presence primarily of iC3b on yeast cells incubated with either normal serum or the reconstituted pathway. Ultrastructural examination of the opsonized yeast cells showed that the cryptococcal capsule was the site for binding of C3 activated from normal serum or the reconstituted pathway, with a dense accumulation of C3 at the periphery of the capsule. Thus, incubation of encapsulated cryptococci in the reconstituted pathway led to deposition of opsonic complement fragments at a site that was appropriate for interaction with phagocyte receptors. Cryptococci opsonized with the reconstituted pathway showed a markedly enhanced interaction with cultured human monocytes compared with unopsonized yeast cells, indicating that the alternative pathway alone is opsonic for yeast cells. However, the results indicate that additional serum factors are needed for optimal opsonization of yeast cells because a 35% reduction in the number of cryptococci bound to macrophages was observed with

  19. Deregulation of Interferon Signaling in Malignant Cells

    Directory of Open Access Journals (Sweden)

    Leonidas C. Platanias

    2010-02-01

    Full Text Available Interferons (IFNs are a family of cytokines with potent antiproliferative, antiviral, and immunomodulatory properties. Much has been learned about IFNs and IFN-activated signaling cascades over the last 50 years. Due to their potent antitumor effects in vitro and in vivo, recombinant IFNs have been used extensively over the years, alone or in combination with other drugs, for the treatment of various malignancies. This review summarizes the current knowledge on IFN signaling components and pathways that are deregulated in human malignancies. The relevance of deregulation of IFN signaling pathways in defective innate immune surveillance and tumorigenesis are discussed.

  20. Material properties in complement activation

    DEFF Research Database (Denmark)

    Moghimi, S. Moein; Andersen, Alina Joukainen; Ahmadvand, Davoud

    2011-01-01

    activation differently and through different sensing molecules and initiation pathways. The importance of material properties in triggering complement is considered and mechanistic aspects discussed. Mechanistic understanding of complement events could provide rational approaches for improved material design...

  1. Aneuploidy-Dependent Massive Deregulation of the Cellular Transcriptome and Apparent Divergence of the Wnt/β-catenin Signaling Pathway in Human Rectal Carcinomas

    Science.gov (United States)

    Grade, Marian; Ghadimi, B. Michael; Varma, Sudhir; Simon, Richard; Wangsa, Danny; Barenboim-Stapleton, Linda; Liersch, Torsten; Becker, Heinz; Ried, Thomas; Difilippantonio, Michael J.

    2016-01-01

    To identify genetic alterations underlying rectal carcinogenesis, we used global gene expression profiling of a series of 17 locally advanced rectal adenocarcinomas and 20 normal rectal mucosa biopsies on oligonucleotide arrays. A total of 351 genes were differentially expressed (P 5-fold difference, and 85 genes always had at least a 2-fold change in all of the matched samples. Twelve genes satisfied all three of these criteria. Altered expression of genes such as PTGS2 (COX-2), WNT1, TGFB1, VEGF, and MYC was confirmed, whereas our data for other genes, like PPARD and LEF1, were inconsistent with previous reports. In addition, we found deregulated expression of many genes whose involvement in rectal carcinogenesis has not been reported. By mapping the genomic imbalances in the tumors using comparative genomic hybridization, we could show that DNA copy number gains of recurrently aneuploid chromosome arms 7p, 8q, 13q, 18q, 20p, and 20q correlated significantly with their average chromosome arm expression profile. Taken together, our results show that both the high-level, significant transcriptional deregulation of specific genes and general modification of the average transcriptional activity of genes residing on aneuploid chromosomes coexist in rectal adenocarcinomas. PMID:16397240

  2. A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission

    DEFF Research Database (Denmark)

    Veszeli, Nóra; Füst, György; Csuka, Dorottya

    2014-01-01

    Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS...

  3. Deposition of mannose-binding lectin and ficolins and activation of the lectin pathway of complement on the surface of polyurethane tubing used for cardiopulmonary bypass.

    Science.gov (United States)

    Eppa, Łukasz; Pągowska-Klimek, Izabela; Świerzko, Anna S; Moll, Maciej; Krajewski, Wojciech R; Cedzyński, Maciej

    2018-04-01

    The artificial surface used for cardiopulmonary bypass (CPB) is a crucial factor activating the complement system and thus contributing to the generation of a systemic inflammatory response. The activation of classical and alternative pathways on this artificial surface is well known. In contrast, lectin pathway (LP) activation has not been fully investigated, although noted during CPB in several studies. Moreover, we have recently proved the contribution of the LP to the generation of the systemic inflammatory response syndrome after pediatric cardiac surgery. The aim of this study was to assess LP-mediated complement activation on the surface of polyurethane CPB circuit tubing (noncoated Chalice ® ), used for CPB procedures in children with congenital heart disease. We found deposition of mannose-binding lectin, ficolin-1, -2, and -3 on the surface of unused tubing and on tubing used for CPB from a small minority of patients. Furthermore, we observed deposition of complement C4 activation products on tubing used for CPB and previously unused tubing after incubation with normal serum. The latter finding indicates LP activation in vitro on the polyurethane surface. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1202-1208, 2018. © 2017 Wiley Periodicals, Inc.

  4. Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.

    Science.gov (United States)

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2012-01-01

    Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

  5. A Metalloproteinase Mirolysin of Tannerella forsythia Inhibits All Pathways of the Complement System

    DEFF Research Database (Denmark)

    Jusko, Monika; Potempa, Jan; Mizgalska, Danuta

    2015-01-01

    Recent reports focusing on virulence factors of periodontal pathogens implicated proteinases as major determinants of remarkable pathogenicity of these species, with special emphasis on their capacity to modulate complement activity. In particular, bacteria-mediated cleavage of C5 and subsequent...... release of C5a seems to be an important phenomenon in the manipulation of the local inflammatory response in periodontitis. In this study, we present mirolysin, a novel metalloproteinase secreted by Tannerella forsythia, a well-recognized pathogen strongly associated with periodontitis. Mirolysin...... with karilysin, as well as a cysteine proteinase of another periodontal pathogen, Prevotella intermedia, resulted in a strong synergistic effect on complement. Furthermore, mutant strains of T. forsythia, devoid of either mirolysin or karilysin, showed diminished survival in human serum, providing further...

  6. Power deregulation in Alberta

    International Nuclear Information System (INIS)

    MacMurchy, N.E.

    1999-01-01

    The impacts of deregulation of the electric power industry in Alberta from the perspective of the natural gas industry was presented with special focus on how the power market can be brought back into balance. The issue of what impacts the deregulated power market will have on natural gas consumption or prices was also reviewed. It was noted that deregulation of the electric power industry will have a definite impact on natural gas consumption but no significant impact on prices. It is estimated that in 1999/2000 gas demand will be 90 million cf/day for incremental electricity generation. However, as long as pipe capacity out of the province exits, this increase in natural gas demand in Alberta is not expected to affect gas prices

  7. Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and Fcγ Receptor Activation Pathways

    Directory of Open Access Journals (Sweden)

    Gina-Maria Lilienthal

    2018-05-01

    Full Text Available IgG antibodies (Abs mediate their effector functions through the interaction with Fcγ receptors (FcγRs and the complement factors. The main IgG-mediated complement activation pathway is induced through the binding of complement C1q to IgG Abs. This interaction is dependent on antigen-dependent hexamer formation of human IgG1 and IgG3 to increase the affinity for the six-headed C1q molecule. By contrast, human IgG4 fails to bind to C1q. Instead, it has been suggested that human IgG4 can block IgG1 and IgG3 hexamerization required for their binding to C1q and activating the complement. Here, we show that murine IgG1, which functionally resembles human IgG4 by not interacting with C1q, inhibits the binding of IgG2a, IgG2b, and IgG3 to C1q in vitro, and suppresses IgG2a-mediated complement activation in a hemolytic assay in an antigen-dependent and IgG subclass-specific manner. From this perspective, we discuss the potential of murine IgG1 and human IgG4 to block the complement activation as well as suppressive effects of sialylated IgG subclass Abs on FcγR-mediated immune cell activation. Accumulating evidence suggests that both mechanisms seem to be responsible for preventing uncontrolled IgG (autoAb-induced inflammation in mice and humans. Distinct IgG subclass distributions and functionally opposite IgG Fc glycosylation patterns might explain different outcomes of IgG-mediated immune responses and provide new therapeutic options through the induction, enrichment, or application of antigen-specific sialylated human IgG4 to prevent complement and FcγR activation as well.

  8. Detection of deregulated modules using deregulatory linked path.

    Directory of Open Access Journals (Sweden)

    Yuxuan Hu

    Full Text Available The identification of deregulated modules (such as induced by oncogenes is a crucial step for exploring the pathogenic process of complex diseases. Most of the existing methods focus on deregulation of genes rather than the links of the path among them. In this study, we emphasize on the detection of deregulated links, and develop a novel and effective regulatory path-based approach in finding deregulated modules. Observing that a regulatory pathway between two genes might involve in multiple rather than a single path, we identify condition-specific core regulatory path (CCRP to detect the significant deregulation of regulatory links. Using time-series gene expression, we define the regulatory strength within each gene pair based on statistical dependence analysis. The CCRPs in regulatory networks can then be identified using the shortest path algorithm. Finally, we derive the deregulated modules by integrating the differential edges (as deregulated links of the CCRPs between the case and the control group. To demonstrate the effectiveness of our approach, we apply the method to expression data associated with different states of Human Epidermal Growth Factor Receptor 2 (HER2. The experimental results show that the genes as well as the links in the deregulated modules are significantly enriched in multiple KEGG pathways and GO biological processes, most of which can be validated to suffer from impact of this oncogene based on previous studies. Additionally, we find the regulatory mechanism associated with the crucial gene SNAI1 significantly deregulated resulting from the activation of HER2. Hence, our method provides not only a strategy for detecting the deregulated links in regulatory networks, but also a way to identify concerning deregulated modules, thus contributing to the target selection of edgetic drugs.

  9. Association between lectin complement pathway initiators, C-reactive protein and left ventricular remodeling in myocardial infarction-a magnetic resonance study

    DEFF Research Database (Denmark)

    Schoos, Mikkel Malby; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole

    2013-01-01

    Lectin complement pathway (LP) activation is an important mechanism in myocardial ischemia reperfusion injury (IRI). LP is activated via the recognition molecules mannose-binding lectin (MBL), ficolins-2 and-3 and is regulated by MBL/Ficolin-associated Protein-1 (MAP-1). Also, C-reactive protein...... (CRP) and ficolin-2 interact in vitro, but the role of the ficolins in IRI is unknown.Methods and results In 55 patients with ST segment elevation myocardial infarction, we investigated the association of LP components and CRP in plasma samples with left ventricular (LV) end systolic and diastolic......-activation in IRI and LV remodeling....

  10. Natural gas and deregulation

    International Nuclear Information System (INIS)

    Maisonnier, G.

    2001-01-01

    The gas market is progressively moving towards new organizations under the effect of the deregulation initiated in the United States, the United Kingdom and transposed to other countries, particularly in Europe, at least for the member countries of the European union. Within the framework provided by this overall trend, Cedigaz proposes this study in order to describe the main developments affecting these markets on account of deregulation. This report is structured on the basis of three main topics (market organization, marketing modes, pricing) which appear to be the most cogent in terms of deregulation. This grouping by major topics accordingly offers a relatively synthetic view of the main trends which could be observed on the European market, for example. Our analysis is largely based on the example of the American market and, to a lesser extent, on the British situation. Whenever possible, concrete examples are provided for a closer understanding of this complex subject. On the whole, deregulation is not a frozen process, but has to adapt permanently to developments in a market stage-managed by politics, the regulator and the industrial players. This obviously means a dynamic and constantly evolving process, making it a highly complex process. This report aims to shed some light on the subject. (author)

  11. Airline Deregulation and Public Policy

    Science.gov (United States)

    Morrison, Steven A.; Winston, Clifford

    1989-08-01

    An assessment of the effects of airline deregulation on travelers and carriers indicates that deregulation has provided travelers and carriers with 14.9 billion of annual benefits (1988 dollars). Airport congestion, airline safety, airline bankruptcy, and mergers are also analyzed and found in most cases to have reduced benefits. But, these costs should not be attributed to deregulation per se, but to failures by the government to pursue appropriate policies in these areas. Pursuit of policies that promote airline competition and efficient use of airport capacity would significantly increase the benefits from deregulation and would provide valuable guidance for other industries undergoing the transition to deregulation.

  12. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    Jackson, M.

    2002-01-01

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  13. Electric deregulation in Canada

    International Nuclear Information System (INIS)

    Way, R.W.

    1996-01-01

    An outline of the electric power deregulation activities across Canada, particularly in Alberta, British Columbia, and Ontario, was presented. A central element of the restructuring is creation of a power pool which acts as an open spot market, and a transmission administrator that provides access to the generators, distribution companies, importers and exporters. Load forecasts, average daily load profile and hourly pool prices for TransAlta Corporation were presented as an example. 22 figs

  14. Natural gas deregulation

    International Nuclear Information System (INIS)

    Ronchi, M.

    1993-01-01

    With the aim of establishing realistic options for deregulation in the natural gas industry, this paper first considers the structural evolution of this industry and evidences how it differs from the petroleum industry with which it exhibits some essential characteristics in common. This comparison is made in order to stress that, contrary to popular belief, that which is without doubt good for the petroleum industry is not necessarily so also for the natural gas industry. The paper concludes with separate analyses of the natural gas markets in the principal industrialized countries. Arguments are provided to show that the 'soft' deregulation option for the natural gas industry is not feasible, and that 'total' deregulation instead, backed by the passing of a suitable package of anti-trust laws 'unbundling' the industry's four major activities, i.e., production, storage, primary and secondary distribution, is the preferable option. The old concept of guaranteed supplies for minor users of natural gas should give way to the laws of supply and demand governing inter-fuel competition ensured through the strict supervision of vigilance committees

  15. The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B

    Science.gov (United States)

    Mendes-Sousa, Antonio F.; do Vale, Vladimir Fazito; Silva, Naylene C. S.; Guimaraes-Costa, Anderson B.; Pereira, Marcos H.; Sant’Anna, Mauricio R. V.; Oliveira, Fabiano; Kamhawi, Shaden; Ribeiro, José M. C.; Andersen, John F.; Valenzuela, Jesus G.; Araujo, Ricardo N.

    2017-01-01

    Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system. PMID:28912782

  16. The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B

    Directory of Open Access Journals (Sweden)

    Antonio F. Mendes-Sousa

    2017-08-01

    Full Text Available Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system.

  17. The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B.

    Science.gov (United States)

    Mendes-Sousa, Antonio F; do Vale, Vladimir Fazito; Silva, Naylene C S; Guimaraes-Costa, Anderson B; Pereira, Marcos H; Sant'Anna, Mauricio R V; Oliveira, Fabiano; Kamhawi, Shaden; Ribeiro, José M C; Andersen, John F; Valenzuela, Jesus G; Araujo, Ricardo N

    2017-01-01

    Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni 2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system.

  18. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation

    Science.gov (United States)

    2012-07-01

    Std. Z39.18 Victoria Seewaldt, M.D. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation Duke University Durham...attomole- zeptomole range. Internal dilution curves insure a high-dynamic calibration range. DU -26 8L DU -26 6L DU -29 5R DU -22 9.2 L DU...3: Nanobiosensor technology is translated to test for pathway deregulation in RPFNA cytology obtained from 10 high-risk women with cytological

  19. Heparin-coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin-2 of the lectin complement pathway in vivo

    DEFF Research Database (Denmark)

    Hein, Estrid; Munthe-Fog, L; Thiara, A S

    2015-01-01

    of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were...... randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, -2 and -3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured......-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures....

  20. LMW-E/CDK2 Deregulates Acinar Morphogenesis, Induces Tumorigenesis, and Associates with the Activated b-Raf-ERK1/2-mTOR Pathway in Breast Cancer Patients

    Science.gov (United States)

    Duong, MyLinh T.; Akli, Said; Wei, Caimiao; Wingate, Hannah F.; Liu, Wenbin; Lu, Yiling; Yi, Min; Mills, Gordon B.; Hunt, Kelly K.; Keyomarsi, Khandan

    2012-01-01

    Elastase-mediated cleavage of cyclin E generates low molecular weight cyclin E (LMW-E) isoforms exhibiting enhanced CDK2–associated kinase activity and resistance to inhibition by CDK inhibitors p21 and p27. Approximately 27% of breast cancers express high LMW-E protein levels, which significantly correlates with poor survival. The objective of this study was to identify the signaling pathway(s) deregulated by LMW-E expression in breast cancer patients and to identify pharmaceutical agents to effectively target this pathway. Ectopic LMW-E expression in nontumorigenic human mammary epithelial cells (hMECs) was sufficient to generate xenografts with greater tumorigenic potential than full-length cyclin E, and the tumorigenicity was augmented by in vivo passaging. However, cyclin E mutants unable to interact with CDK2 protected hMECs from tumor development. When hMECs were cultured on Matrigel, LMW-E mediated aberrant acinar morphogenesis, including enlargement of acinar structures and formation of multi-acinar complexes, as denoted by reduced BIM and elevated Ki67 expression. Similarly, inducible expression of LMW-E in transgenic mice generated hyper-proliferative terminal end buds resulting in enhanced mammary tumor development. Reverse-phase protein array assay of 276 breast tumor patient samples and cells cultured on monolayer and in three-dimensional Matrigel demonstrated that, in terms of protein expression profile, hMECs cultured in Matrigel more closely resembled patient tissues than did cells cultured on monolayer. Additionally, the b-Raf-ERK1/2-mTOR pathway was activated in LMW-E–expressing patient samples, and activation of this pathway was associated with poor disease-specific survival. Combination treatment using roscovitine (CDK inhibitor) plus either rapamycin (mTOR inhibitor) or sorafenib (a pan kinase inhibitor targeting b-Raf) effectively prevented aberrant acinar formation in LMW-E–expressing cells by inducing G1/S cell cycle arrest. LMW

  1. Complement Test

    Science.gov (United States)

    ... Salicylates Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia ... and forming complexes that respond to infections, non-self tissues (transplants), dead cells ... KJ. Complement determinations in human disease. Ann Allergy Asthma Immunol . 2004; ...

  2. Surface-bound capsular polysaccharide of type Ia group B Streptococcus mediates C1 binding and activation of the classic complement pathway

    International Nuclear Information System (INIS)

    Levy, N.J.; Kasper, D.L.

    1986-01-01

    The role of surface-bound type Ia group B Streptococcus (GBS) capsular polysaccharide in anti-body-independent binding of C1 and activation of the classic component pathway was investigated. In a radiolabeled bacterial-polymorphonuclear leukocyte (PMN) association assay, a measure of bacterial opsonization, preincubation of 3 H-type Ia GBS with purified F(ab') 2 to the organism blocked the association of the bacteria with PMN', and the inhibitory effect was dose dependent. The specificity of F(ab') 2 blocking was shown after adsorption of F(ab') 2 with type Ia polysaccharide-sensitized erythrocytes. Polysaccharide-adsorbed F(ab') 2 had a 70% decrease in ability to block the association of bacteria with PMN. Neuraminidase digestion removed 80% of the terminal sialic acid residues from the native polysaccharide. These neuraminidase-digested organisms had a 72% decrease in binding and transfer of purified C1 compared with non-enzyme-treated organisms. Type Ia capsular polysaccharide bound to sheep erythrocytes promoted classic complement pathway-mediated hemolysis of the cells. The role of C1 inhibitor (INH) in modulation of C1 activation by the organisms was investigated. The possibility existed that the C1 INH could be bound by the bacteria, allowing C1 activation to occur in the fluid phase. The inhibitor was purified from human serum, and its activity was measured before and after incubation with type Ia GBS. The organisms had no effect on C1 INH activity. Thus surface-bound capsular polysacchardie of type Ia GBS mediates C1 binding and classic pathway activation, and this does not involve the C1 INH

  3. Complement Evasion by Pathogenic Leptospira.

    Science.gov (United States)

    Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

    2016-01-01

    Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira . Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira , have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host.

  4. Studies of the binding of ficolin-2 and ficolin-3 from the complement lectin pathway to Leptospira biflexa, Pasteurella pneumotropica and Diarrheagenic Escherichia coli

    DEFF Research Database (Denmark)

    Sahagún-Ruiz, Alfredo; Breda, Leandro Carvalho Dantas; Valencia, Mónica Marcela Castiblanco

    2015-01-01

    Ficolins recognize pathogen associated molecular patterns and activate the lectin pathway of complement system. However, our knowledge regarding pathogen recognition of human ficolins is still limited. We therefore set out to explore and investigate the possible interactions of the two main serum...

  5. Utility deregulation and AMR technology

    International Nuclear Information System (INIS)

    Moore, G.

    1991-01-01

    This article reviews the effects of deregulation on other utilities and services and examines how the electric utilities can avoid the worst of these effects and capitalize of the best aspects of competition in achieving marketing excellence. The article presents deregulation as a customer service and underscores the need for utilities to learn to compete aggressively and intelligently and provide additional services available through technology such as automated meter reading

  6. BF*F allotype of the alternative pathway of complement: A marker of protection against the development of antiphospholipid antibodies in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Picceli, V F; Skare, T L; Nisihara, R M; Nass, F R; Messias-Reason, I T; Utiyama, S R R

    2016-04-01

    B factor (BF) from the alternative complement pathway seems to participate in the pathophysiology of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). To study the allotypic variability of BF in SLE and their associations with clinical and autoantibodies profile. BF allotypes were determined by high-voltage agarose gel electrophoresis, under constant cooling, followed by immunofixation with anti-human BF antibody, in 188 SLE patients and 103 controls. Clinical and serological data were obtained from medical examination and records. No significant differences of BF variants between patients and controls were found, neither in relation to epidemiologic or clinical manifestations. Associations of phenotype BF SS07 and allotype BF*S07 were found with anticardiolipin IgM (aCl-IgM) antibodies (p = 0.014 and p = 0.009 respectively), but not with aCl-IgG, lupus anticoagulant (LA), anti β2GPI or clinical APS. A significant decrease in BF*F allotype (p = 0.043) and BF SF phenotype (p = 0.018) was detected in patients with anti-phospholipid antibodies as a whole (aCl-IgG, aCl-IgM, LA and anti β2GPI). There is a link between phenotype BF SS07 and allotype BF*S07 with aCl-IgM in SLE patients; BF*F allotype could be considered a marker of protection against the development of antiphospholipid antibodies in these patients. © The Author(s) 2015.

  7. The undertow of deregulation : reregulation

    International Nuclear Information System (INIS)

    Bradford, J.A.

    2003-01-01

    Alberta, Ontario and New Brunswick each initiated measures to deregulate their electric power industries in order to remain competitive with lower electricity rates in some U.S. states where the industry was also moving towards deregulation. This paper considers how the original sweep of deregulation policy goals succumbed to electricity reregulation policies. The decision by British Columbia to re-examine its deregulation plans in light of the experience in Canada's 3 other province's was also examined. The paper describes the electric power industry from 1900 to 1960s, before the deregulation wave hit the industry. It then proceeds to the 1970s which was marked by the oil embargo. The 1980s saw a new era of policy shifts towards deregulation and privatization activity which was intended to introduce competition into regulated industries. Alberta was the first Canadian province to introduce competition to its electricity industry in an effort to remain competitive with neighbouring U.S. jurisdictions. By the 1990s Ontario's vertically integrated electricity industry was in trouble and recommendations were made to dissolve Ontario's Hydro One monopoly, particularly in power generation. In 1999, New Brunswick restructured its electricity industry to remain competitive with New England's electricity industry. The paper describes the gradual pull back from deregulation by all 3 provinces and the measures taken to impose price controls. Both industry and consumers paid a price for major policy changes. Complete competition in New Brunswick never materialized. It was suggested that controlled competition will likely move the electricity industry in the future. 40 refs

  8. Environmental impact of electricity deregulation

    International Nuclear Information System (INIS)

    Swisher, Joel N.; McAlpin, Maria C.

    2006-01-01

    Restructuring of electric utilities affects environmental quality primarily through its effect on airborne emissions. We examine emissions from 1993 to 2002 and discuss possible explanatory factors. Annual NOx and SO 2 emissions fell nationally, mostly due to decreases in emission limits driven by state and Federal regulations. CO 2 emissions have increased almost proportionately with increased generation. Generation increased more than it would have, partly due to energy efficiency spending reductions that accompanied deregulation. The fuel mix shifted slightly from coal to gas, offsetting some CO 2 emissions increases and contributing to SO 2 and NOx emissions decreases. While the percentage share of generation from renewable sources remained at about 2%, recent and expected future increases in wind generating capacity promise future emissions reductions. Although deregulation lacks clear environmental advantages, the deregulation process creates an opportunity for implementation of state policies to reduce emissions. Regulated and deregulated states with renewable portfolio standards (RPS) have a higher average percent of generation from renewable sources. Average energy efficiency savings are higher in regulated states, but slightly higher in deregulated states with a system benefits charge (SBC) than in regulated states without a SBC

  9. Deregulation - a source of crisis?

    International Nuclear Information System (INIS)

    Haavardstein, Hilde; Sandsmark, Maria

    2003-01-01

    Since the beginning of the 1990s, deregulation has become widespread in many of the worlds power markets. When it is no longer the authorities, but the players in the market who are deciding on investments in new production capacity, on the basis of business economic estimates of profitability, it is important that the external conditions are worked out such that they provide incentives to investments of the right extent and to the right time. Examples from deregulated markets show that the formulation of such external frames has contributed to a tight power balance

  10. Deregulation and Macroeconomic Drivers Of Foreign Direct ...

    African Journals Online (AJOL)

    Deregulation and Macroeconomic Drivers Of Foreign Direct Investment In Nigerian Agriculture (1970 -2009): An Econometric Analysis. ... The study showed that foreign exchange and the economic deregulation policy of Nigerian government ...

  11. Energy deregulation: the Vattenfall experience

    International Nuclear Information System (INIS)

    Nyquist, C.E.

    1999-01-01

    In 1992, Sweden prepared itself for deregulation by transforming Vattenfall, the country's main supplier of energy, from a public utility into a limited liability company. Vattenfall was still 100% owned by the state, but began to operate as a commercial entity with a separate board of directors. On January 1, 1996, Sweden and Finland deregulated, and the three Nordic countries - Norway, Sweden and Denmark - became a completely open market. Beginning November 1, 1999, Sweden will introduce simplified metering, bringing competition directly to consumers, which represents the purest and most advanced form of electricity competition, forcing Vattenfall and its peers to fight for the loyalty of customers from the smallest retail household upwards. As a central participant in deregulation, Vattenfall was faced with some major challenges. In essence, Vattenfall had to evolve from a parochial Swedish public utility into a pan-European energy services company. The transition was successful and Vattenfall today represents about 20% of Scandinavia's generation capacity, with operations that are about 1/2 the size of those of Ontario Hydro. Vattenfall had to take a number of steps to get ready for a fully competitive retail market. First it established a market oriented group organization based on three units: Vattenfall Electricity Generation, Vattenfall Energy Market, and Vattenfall Electricity Networks and Services. Second it expanded its relationship with its customers. Third it adjusted to the fact that electricity deregulation led to an immediate generation surplus. The main lessons learned from the experience are summarized

  12. Deregulation of brain insulin signaling in Alzheimer's disease.

    Science.gov (United States)

    Chen, Yanxing; Deng, Yanqiu; Zhang, Baorong; Gong, Cheng-Xin

    2014-04-01

    Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.

  13. Deregulation of Lesotho's maize market

    OpenAIRE

    van Schalkwyk, Herman D.; van Zyl, Johan; Botha, P.W.; Bayley, B.

    1997-01-01

    During the past year, there have been major policy reforms in Lesotho and South Africa with respect to maize pricing and marketing. In Lesotho the impact of deregulation on producers, consumers and government revenues was substantially lower than it should have been, and as a result Lesotho was not able to reap the full benefits of these changes. This is partly because information on the changes to the maize marketing system did not reach the potential beneficiaries of the new system. Free an...

  14. Lowering electricity prices through deregulation

    OpenAIRE

    Thomas Klitgaard; Rekha Reddy

    2000-01-01

    A wave of regulatory reform is now transforming the U.S. electricity industry. As state and federal authorities allow independent power producers to compete with utilities in supplying electricity, consumers are paying close attention to the effects of this change on their energy bills. Although deregulation poses significant structural challenges, the introduction of competitive pressures should ultimately lead to efficiency gains for the industry and cost savings for households and businesses.

  15. Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet.

    Science.gov (United States)

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Rehfeldt, Charlotte; Metges, Cornelia C

    2011-12-01

    Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.

  16. Deregulator: Judgment Day for microeconomics

    International Nuclear Information System (INIS)

    Keen, S.

    2004-01-01

    The economic theory that motivated the deregulation and privatization of the US electricity industry is seriously flawed in three crucial ways. First, the Marshallian theory of the firm is based on two mathematical errors which, when amended, reverse the accepted welfare rankings of competitive and monopoly industry structures: on the grounds of corrected neoclassical theory, monopoly should be preferred to competition. Second, while proponents of deregulation expected market-clearing equilibrium prices to apply, it is well known that the equilibrium of a system of spot market prices is unstable. This implies that imposing spot market pricing on as basic an industry as electricity is likely to lead to the kind of volatility observed under the deregulation. Third, extensive empirical research has established that on the order of 95% of firms do not produce under conditions of rising marginal cost. Requiring electricity firms to price at marginal cost was therefore likely to lead to bankruptcies, as indeed occurred. The economic preference for marginal cost spot market pricing is therefore theoretically unsound, and it is no wonder that the actual deregulatory experience was as bad as it was. (author)

  17. Deregulator: Judgment Day for microeconomics

    Energy Technology Data Exchange (ETDEWEB)

    Keen, S. [University of Western Sydney, Penrith (Australia). School of Economics and Finance

    2004-09-01

    The economic theory that motivated the deregulation and privatization of the US electricity industry is seriously flawed in three crucial ways. First, the Marshallian theory of the firm is based on two mathematical errors which, when amended, reverse the accepted welfare rankings of competitive and monopoly industry structures: on the grounds of corrected neoclassical theory, monopoly should be preferred to competition. Second, while proponents of deregulation expected market-clearing equilibrium prices to apply, it is well known that the equilibrium of a system of spot market prices is unstable. This implies that imposing spot market pricing on as basic an industry as electricity is likely to lead to the kind of volatility observed under the deregulation. Third, extensive empirical research has established that on the order of 95% of firms do not produce under conditions of rising marginal cost. Requiring electricity firms to price at marginal cost was therefore likely to lead to bankruptcies, as indeed occurred. The economic preference for marginal cost spot market pricing is therefore theoretically unsound, and it is no wonder that the actual deregulatory experience was as bad as it was. (author)

  18. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patie...

  19. Did Globalization Influence Credit Market Deregulation

    OpenAIRE

    Eppinger, Peter; Potrafke, Niklas

    2015-01-01

    We investigate whether globalization influenced credit market deregulation over the period 1970-2010. Globalization is measured by the KOF indices of globalization. Credit market deregulation is measured by the credit market freedom indicators of the Fraser Institute. The results from both cross-sectional and panel regressions using ordinary least squares indicate a positive correlation between globalization and credit market deregulation. We account for reverse causality by using predicted t...

  20. Product Market Deregulation and Employment Outcomes

    OpenAIRE

    Senftleben-König, Charlotte

    2014-01-01

    This paper investigates the short- and medium-term effects of the deregulation of shopopening hours legislation on retail employment in Germany. In 2006, the legislative competence was shifted from the federal to the state level, leading to a gradual deregulation of shop opening restrictions in most of Germany’s sixteen federal states. The paper exploits regional variation in the legislation in order to identify the effect product market deregulation has on retail employment. We find robust e...

  1. Deregulation, a challenge for regulators

    International Nuclear Information System (INIS)

    Alonso, Augustin

    2001-01-01

    Deregulation and competitiveness in the electricity market invites the plant owner/operator to reduce operating cost with a potential reduction in maintenance, degradation of investment in safety, reduction of operating staff and a downgrading in research and development. On the other side, deregulation and competitiveness brings the social and industrial benefit of reducing the electricity cost. Regulatory organisations have to watch that the safety level of the plant does not go beyond the established level, while recognising the benefits of the new situation; therefore they have the moral responsibility of regulating nuclear energy effectively and efficiently and in eliminating unnecessary regulatory burdens. Regulation has evolved with time and in accordance with the knowledge gained from research and the analysis of operating experience. The knowledge gained has made it possible to follow the path of other modern advanced technologies, where risk is quantified and the system approved when the risk becomes lower than an accepted level. The regulatory use of this advanced tool is being now developed by the most advanced regulatory organisations, under the name of risk informed regulation, where the reference level is the expected frequency of core damage. Deregulation and competitiveness will not change the basis of the already well established procedure to verify compliance. Nevertheless, the contents of Safety Analysis Reports and other regulatory documents, such as Technical Specifications for Operation, offer room for improvement in the sense of being more to the roots of the matter and becoming more efficient tools in the verification process. The contents of these documents have been evolving along the time and they have become unnecessary voluminous and rather burdensome. Much work has been done to improve the efficiency of regulatory inspections by concentrating on basic aspects. As a partial application of the already mentioned risk-informed regulation

  2. Sodium polyanethole sulfonate as an inhibitor of activation of complement function in blood culture systems

    DEFF Research Database (Denmark)

    Palarasah, Yaseelan; Skjoedt, Mikkel-Ole; Vitved, Lars

    2010-01-01

    complement activation pathways: the classical, alternative, and lectin pathways, respectively. Inhibition of complement activity by SPS is caused by a blocking of complement activation and is not a result of complement consumption. The classical pathway is inhibited at SPS concentrations greater than 0.1 mg...... findings also open up the possibility of a new assay for the assessment of the functional capacity of the lectin complement pathway....

  3. Deregulation impacts AMR business cases

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, M.; Fauth, G.

    2001-09-01

    Meter reading strategy is being affected in fundamental ways by deregulation. For the utilities attempting to cope with meter reading unbundling, the processes, insights and general rules that had been developed prior to 2000 in the field of Automatic Meter Reading can no longer be relied upon to provide useful lessons. The fundamental impact on Automatic Meter Reading (AMR) business case drivers and the increasing complexity of building the business case model result from deregulation and unbundling. More and more, management has come to rely on rigorous business case analysis to compensate for the magnitude of AMR projects on the utility and the scarcity of financial resources. One can now expect the Chief Financial Officer and the Vice President Finance to become active players on AMR project teams in the fields of business case scrutiny and approval. Increasingly, the normal expertise of AMR personnel does not suffice to build a business case acceptable to finance. The financial and economic analysis skills required are ever more complex.

  4. Complement C5a-C5aR interaction enhances MAPK signaling pathway activities to mediate renal injury in trichloroethylene sensitized BALB/c mice.

    Science.gov (United States)

    Zhang, Jia-xiang; Zha, Wan-sheng; Ye, Liang-ping; Wang, Feng; Wang, Hui; Shen, Tong; Wu, Chang-hao; Zhu, Qi-xing

    2016-02-01

    We have previously shown complement activation as a possible mechanism for trichloroethylene (TCE) sensitization, leading to multi-organ damage including the kidneys. In particular, excessive deposition of C5 and C5b-9-the membrane attack complex, which can generate significant tissue damage, was observed in the kidney tissue after TCE sensitization. The present study tested the hypothesis that anaphylatoxin C5a binding to its receptor C5aR mediates renal injury in TCE-sensitized BALB/c mice. BALB/c mice were sensitized through skin challenge with TCE, with or without pretreatment by the C5aR antagonist W54011. Kidney histopathology and the renal functional test were performed to assess renal injury, and immunohistochemistry and fluorescent labeling were carried out to assess C5a and C5aR expressions. TCE sensitization up-regulated C5a and C5aR expressions in kidney tissue, generated inflammatory infiltration, renal tubule damage, glomerular hypercellularity and impaired renal function. Antagonist pretreatment blocked C5a binding to C5aR and attenuated TCE-induced tissue damage and renal dysfunction. TCE sensitization also caused the deposition of major pro-inflammatory cytokines IL-2, TNF-α and IFN-γ in the kidney tissue (P < 0.05); this was accompanied by increased expression of P-p38, P-ERK and P-JNK proteins (P < 0.05). Pretreatment with the C5aR antagonist attenuated the increase of expression of P-p38, P-ERK and P-JNK proteins (P < 0.05) and also consistently reduced the TCE sensitization-induced increase of IL-2, TNF-α and IFN-γ (P < 0.05). These data identify C5a binding to C5aR, MAP kinase activation, and inflammatory cytokine release as a novel mechanism for complement-mediated renal injury by sensitization with TCE or other environmental chemicals. Copyright © 2015 John Wiley & Sons, Ltd.

  5. CSF coccidioides complement fixation

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003526.htm CSF coccidioides complement fixation test To use the sharing features on this page, please enable JavaScript. CSF coccidioides complement fixation is a test that checks ...

  6. Power Buying: Planning For Your Deregulated Future.

    Science.gov (United States)

    Robertson, Wayne K.

    1997-01-01

    Colleges and universities can benefit from the coming deregulation of utilities. Deregulation creates opportunity for facility managers to aggressively negotiate agreements, implement changes to the physical plant to make the institution a more attractive customer, and explore new, less expensive energy supply options and alternatives. Some action…

  7. Economic and Environmental Effects of Airline Deregulation

    NARCIS (Netherlands)

    Schipper, Youdi; Rietveld, Piet

    1997-01-01

    This paper deals with the issue of regulatory reform in the airline industry, in connection with environmental externalities. Deregulation has led to shorter routes, higher frequencies, probably larger aircraft sizes and more intense peak traffic at airports. In addition, deregulation has led to

  8. Deregulation: Implications for Community College Leaders.

    Science.gov (United States)

    Bender, Louis W.

    1986-01-01

    Looks at the ways in which the deregulation of business and industry may affect community colleges in the years ahead, using the banking industry as an illustration. Argues that the deregulation of higher education requires that community college leadership programs examine past assumptions and develop new strategies. (LAL)

  9. Shark complement: an assessment.

    Science.gov (United States)

    Smith, S L

    1998-12-01

    The classical (CCP) and alternative (ACP) pathways of complement activation have been established for the nurse shark (Ginglymostoma cirratum). The isolation of a cDNA clone encoding a mannan-binding protein-associated serine protease (MASP)-1-like protein from the Japanese dogfish (Triakis scyllia) suggests the presence of a lectin pathway. The CCP consists of six functionally distinct components: C1n, C2n, C3n, C4n, C8n and C9n, and is activated by immune complexes in the presence of Ca++ and Mg++ ions. The ACP is antibody independent, requiring Mg++ ions and a heat-labile 90 kDa factor B-like protein for activity. Proteins considered homologues of C1q, C3 and C4 (C2n) of the mammalian complement system have been isolated from nurse shark serum. Shark C1q is composed of at least two chain types each showing 50% identity to human C1q chains A and B. Partial sequence of the globular domain of one of the chains shows it to be C1q-like rather than like mannan-binding protein. N-terminal amino acid sequences of the alpha and beta chain of shark C3 and C4 molecules show significant identity with corresponding human C3 and C4 chains. A sequence representing shark C4 gamma chain, shows little similarity to human C4 gamma chain. The terminal shark components C8n and C9n are functional analogues of mammalian C8 and C9. Anaphylatoxin activity has been demonstrated in activated shark serum, and porcine C5a desArg induces shark leucocyte chemotaxis. The deduced amino acid sequence of a partial C3 cDNA clone from the nurse shark shows 50%, 30% and 24% homology with the corresponding region of mammalian C3, C4 and alpha 2-macroglobulin. Deduced amino acid sequence data from partial Bf/C2 cDNA clones, two from the nurse shark and one from the Japanese dogfish, suggest that at least one species of elasmobranch has two distinct Bf/C2 genes.

  10. Energy deregulation: lessons from the American experience

    International Nuclear Information System (INIS)

    Chiam, L.

    1997-01-01

    This article presents a brief history of US energy regulation, considers some of the important issues arising from the US experience and finally, suggests some lessons which Australia might draw from the US deregulation of energy industries. 5 refs

  11. Power system deregulation and the Balkan countries

    International Nuclear Information System (INIS)

    Glamochanin, Vlastimir; Stojkovska, Biljana; Cherepnalkoski, Trajche

    2001-01-01

    The aim of the paper is to show the current state and planned activities of the Power System deregulation and privatization in the following Balkan countries: Macedonia, Romania, Bulgaria, Yugoslavia, Greece, Croatia, Slovenia and Turkey

  12. Banking deregulation and corporate tax avoidance

    Directory of Open Access Journals (Sweden)

    Bill B. Francis

    2017-06-01

    Full Text Available We investigate whether tax avoidance substitutes for external financing. We exploit interstate banking deregulation as a quasi-external shock to examine whether firms engage in less tax avoidance after banking deregulation, because of cheaper and easier access to credit from banks. We find no empirical evidence to support this substitutive relation, even for firms with higher financial constraints or firms with higher external financing dependence.

  13. Implications of U.S. electricity deregulation

    International Nuclear Information System (INIS)

    Gottfried, D.A.

    1997-01-01

    This article is a concise summary of the potential impacts of electric utility deregulation, including the resolution of stranded costs, impact on electricity rates, reformation of utilities, and reshuffling of the nation's fuel portfolio. The national and state implications of the deregulation of the electricity industry are monumental and overwhelming. The implications occur on many fronts, including monetary, quality, reliability, and environmental issues. Many significant changes will occur as a result--some will be positive and others may be more disturbing

  14. Surviving mousepox infection requires the complement system.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Moulton

    2008-12-01

    Full Text Available Poxviruses subvert the host immune response by producing immunomodulatory proteins, including a complement regulatory protein. Ectromelia virus provides a mouse model for smallpox where the virus and the host's immune response have co-evolved. Using this model, our study investigated the role of the complement system during a poxvirus infection. By multiple inoculation routes, ectromelia virus caused increased mortality by 7 to 10 days post-infection in C57BL/6 mice that lack C3, the central component of the complement cascade. In C3(-/- mice, ectromelia virus disseminated earlier to target organs and generated higher peak titers compared to the congenic controls. Also, increased hepatic inflammation and necrosis correlated with these higher tissue titers and likely contributed to the morbidity in the C3(-/- mice. In vitro, the complement system in naïve C57BL/6 mouse sera neutralized ectromelia virus, primarily through the recognition of the virion by natural antibody and activation of the classical and alternative pathways. Sera deficient in classical or alternative pathway components or antibody had reduced ability to neutralize viral particles, which likely contributed to increased viral dissemination and disease severity in vivo. The increased mortality of C4(-/- or Factor B(-/- mice also indicates that these two pathways of complement activation are required for survival. In summary, the complement system acts in the first few minutes, hours, and days to control this poxviral infection until the adaptive immune response can react, and loss of this system results in lethal infection.

  15. Stable GPR101 over-Expressing Cell Lines As an Invaluable Tool for Functional Studies, Ligand Screening, and the Identification of Deregulated Genes/Pathways in Patients with X-Linked Acrogigantism

    OpenAIRE

    Trivellin, Giampaolo; Janjic, Maria; Larco, Darwin; Tomic, Melanija; Daly, Adrian; Palmeira, Leonor; Faucz; BECKERS, Albert; Wu, T John; Calebiro, Davide; Stojilkovic, Stanko; Stratakis, Constantine

    2017-01-01

    Background: GPR101 is an orphan G protein-coupled receptor (GPCR) that is duplicated in patients with X-linked acrogigantism (X-LAG) and over-expressed in their GH- and PRL-secreting tumors. GPR101 is a constitutively active GPCR that strongly activates the cAMP pathway. To elucidate the mechanisms through which GPR101 causes GH over-secretion we generated HEK293 and GH/PRL-secreting (GH3) cells with stable GPR101 expression. Methods: Both cell lines were created via direct integration of ...

  16. Consequences of electricity deregulation on nuclear safety

    International Nuclear Information System (INIS)

    Podjavorsek, M.

    2007-01-01

    The evolution of deregulation of electricity market started a couple of years ago and has not been finished yet. Deregulation causes increased pressure to reduce the costs of electricity generation. This presents a new challenge to regulatory bodies. They have to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the deregulation. Today's trend is that the number of electricity generating power companies will be reduced in Europe and also in Slovenia due to tough competition in the electricity market. The electricity price has decreased after the introduction of the deregulated market in most countries. This has been also the main reason for less investment to new generating capacities since the price has been lower than the generation costs. Investment problems are also present for the existing units, because of danger of inappropriate maintenance and reduction of the number of staff and their qualifications below the desired level that leads to loss of institutional memory. It is expected that only the biggest companies can stand the consequences of competition in electricity prices and consequential pressure to reduce the cost. In order to review the impact of deregulation of the electricity market some relevant points are discussed in this paper such as the need to cut costs of companies by reducing the number of their activities and increasing the efficiency in the remaining activities and /or outsourcing of activities, power station operating regime, safety culture, grid reliability, reliability and safety of operation, increased number of transients, ageing of components, outage duration, extended cycle and response of nuclear regulators. From a regulatory point of view the impact of deregulation on nuclear safety is an important issue. This paper also discusses analyses and evaluations of this impact and proposes some measures how to

  17. Two factors of the lectin pathway of complement, l-ficolin and mannan-binding lectin, and their associations with prematurity, low birthweight and infections in a large cohort of Polish neonates.

    Science.gov (United States)

    Swierzko, Anna St; Atkinson, Anne P M; Cedzynski, Maciej; Macdonald, Shirley L; Szala, Agnieszka; Domzalska-Popadiuk, Iwona; Borkowska-Klos, Monika; Jopek, Aleksandra; Szczapa, Jerzy; Matsushita, Misao; Szemraj, Janusz; Turner, Marc L; Kilpatrick, David C

    2009-02-01

    Ficolins and one collectin, mannan-binding lectin (MBL), are the only factors known to activate the lectin pathway (LP) of complement. There is considerable circumstantial evidence that MBL insufficiency can increase susceptibility to various infections and influence the course of several non-infectious diseases complicated by infections. Much less information is available concerning l-ficolin. We report the results of a prospective study to investigate any association between either MBL deficiency or l-ficolin deficiency with prematurity, low birthweight or perinatal infections in a large cohort of Polish neonates, representing an ethnically homogenous population (n=1832). Cord blood samples were analysed to determine mbl-2 gene variants, MBL concentrations and MBL-MASP-2 complex activities (MBL-dependent lectin pathway activity) as well as l-ficolin levels. Median concentrations of l-ficolin and MBL were 2500 and 1124 ng/ml, respectively, while median LP activity was 272 mU/ml. After genotyping, 60.6% of babies were mbl-2 A/A, 35.4% were A/O and 4% were O/O genotypes. We found relative l-ficolin deficiency to be associated with prematurity, low birthweight and infections. l-Ficolin concentration correlated with gestational age and with birthweight, independently of gestational age. Preterm deliveries (prematurity. Our findings suggest that l-ficolin participates in host defence during the perinatal period and constitute the first evidence that relative l-ficolin deficiency may contribute to the adverse consequences of prematurity. Some similar trends were found with facets of MBL deficiency, but the observed relationships were weaker and less consistent.

  18. Bitter gourd (Momordica charantia) as a rich source of bioactive components to combat cancer naturally: Are we on the right track to fully unlock its potential as inhibitor of deregulated signaling pathways.

    Science.gov (United States)

    Farooqi, Ammad Ahmad; Khalid, Sumbul; Tahir, Fatima; Sabitaliyevich, Uteuliev Yerzhan; Yaylim, Ilhan; Attar, Rukset; Xu, Baojun

    2018-05-10

    Research over decades has progressively explored pharmacological actions of bitter gourd (Momordica charantia). Biologically and pharmacologically active molecules isolated from M. charantia have shown significant anti-cancer activity in cancer cell lines and xenografted mice. In this review spotlight was set on the bioactive compounds isolated from M. charantia that effectively inhibited cancer development and progression via regulation of protein network in cancer cells. We summarize most recent high-quality research work in cancer cell lines and xenografted mice related to tumor suppressive role-play of M. charantia and its bioactive compounds. Although M. charantia mediated health promoting, anti-diabetic, hepatoprotective, anti-inflammatory effects have been extensively investigated, there is insufficient information related to regulation of signaling networks by bioactive molecules obtained from M. charantia in different cancers. M. charantia has been shown to modulate AKT/mTOR/p70S6K signaling, p38MAPK-MAPKAPK-2/HSP-27 pathway, cell cycle regulatory proteins and apoptosis-associated proteins in different cancers. However, still there are visible knowledge gaps related to the drug targets in different cancers because we have not yet developed comprehensive understanding of the M. charantia mediated regulation of signal transduction pathways. To explore these questions, experimental platforms are needed that can prove to be helpful in getting a step closer to personalized medicine. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. The Lectin Pathway of Complement and Biocompatibility

    DEFF Research Database (Denmark)

    Hein, Estrid; Garred, Peter

    2015-01-01

    In modern health technologies the use of biomaterials in the form of stents, haemodialysis tubes, artificial implants, bypass circuits etc. is rapidly expanding. The exposure of synthetic, foreign surfaces to the blood and tissue of the host, calls for strict biocompatibility in respect to contac...

  20. Deregulating electricity in the American states

    Science.gov (United States)

    Terbush, Thomas Lee

    This dissertation develops nine stylized facts that summarize the major consequences of deregulation and tests these against recent experience in the electric utility industry. The experience of the electric utility industry matches the predictions of the stylized facts, except in one instance: although real electricity prices fell between 1982 and 1999, real prices fell less in states that deregulated. This dissertation presents three possible explanations for this discrepancy. First, through dynamic efficiency, consumers may benefit in the long run through lower rates and better service in the electricity market, or deregulation may be a public good that benefits electricity consumers through economy-wide improvements in efficiency. Second, higher prices may be a long-run outcome as predicted by the theory of the second best. Or third, both regulators and utilities may use deregulation to generate new rents. Because the original rents from regulation had dissipated, new rents could be generated under deregulation by making consumers pay off the utilities and then creating more new rents through re-regulation of the industry. Close examination tends to support the first and third explanations, although the second-best explanation cannot yet be ruled out completely. Higher prices appear to be a transitional phenomenon, resulting from a short-term payoff from consumers to incumbent utilities that was required to move deregulation forward. This payoff occurs as residential and commercial consumers bear relatively higher rates over three to five years to compensate utilities for stranded costs, investments thought to be unrecoverable under full competition. All states are benefiting from deregulation, but states that are deregulating are benefiting less while stranded costs are being recovered. This dissertation also examines California electricity deregulation and finds that the experience in California conforms with to the stylized facts, and that certain structural

  1. Deregulated power prices: comparison of diurnal patterns

    International Nuclear Information System (INIS)

    Ying Li; Flynn, P.C.

    2004-01-01

    We examine electrical power price, and in particular its daily and average weekday vs. weekend pattern of change, for 14 deregulated markets. Power price in deregulated markets shows fundamentally different patterns. North American markets show a monotonic diurnal weekday price pattern, while all other markets studied show more than one price peak. Deregulated power markets differ in maximum vs. minimum daily average price and in average weekday to weekend price, in turn creating a different incentive for a consumer to time shift power consuming activities. Markets differ in the extent to which a small fraction of the days shapes the average diurnal pattern and value of price. Deregulated markets show a wide variation in the correlation between load and price. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent, and hence that can encourage a customer to shape consumption behaviors. Other markets, for example South Australia, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to escape risk through hedging mechanisms. (Author)

  2. Deregulated power prices: comparison of diurnal patterns

    International Nuclear Information System (INIS)

    Li Ying; Flynn, Peter C.

    2004-01-01

    We examine electrical power price, and in particular its daily and average weekday vs. weekend pattern of change, for 14 deregulated markets. Power price in deregulated markets shows fundamentally different patterns. North American markets show a monotonic diurnal weekday price pattern, while all other markets studied show more than one price peak. Deregulated power markets differ in maximum vs. minimum daily average price and in average weekday to weekend price, in turn creating a different incentive for a consumer to time shift power consuming activities. Markets differ in the extent to which a small fraction of the days shapes the average diurnal pattern and value of price. Deregulated markets show a wide variation in the correlation between load and price. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent, and hence that can encourage a customer to shape consumption behaviors. Other markets, for example South Australia, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to escape risk through hedging mechanisms

  3. Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients

    DEFF Research Database (Denmark)

    Anvar, Seyed Yahya; hoen, Peter Ac; Venema, Andrea

    2011-01-01

    molecular pathways that are consistently associated with OPMD, we performed an integrated high-throughput transcriptome study in affected muscles of OPMD animal models and patients. The ubiquitin-proteasome system (UPS) was found to be the most consistently and significantly OPMD-deregulated pathway across...

  4. Autocrine Effects of Tumor-Derived Complement

    Directory of Open Access Journals (Sweden)

    Min Soon Cho

    2014-03-01

    Full Text Available We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

  5. Transmission planning in a deregulated environment

    DEFF Research Database (Denmark)

    Xu, Zhao

    2006-01-01

    The worldwide trend for the deregulation of the electricity generation and transmission industries has led to dramatic changes in system operation and planning procedures. The optimum approach to transmission-expansion planning in a deregulated environment is an open problem especially when the r...... electricity market grid are performed. In addition, the proposed method is compared with a traditional planning method to further verify its effectiveness....... the responsibilities of the organisations carrying out the planning work need to be addressed. To date there is a consensus that the system operator and network manager perform the expansion planning work in a centralised way. However, with an increasing input from the electricity market, the objectives, constraints...... and approaches toward transmission planning should be carefully designed to ensure system reliability as well as meeting the market requirements. A market-oriented approach for transmission planning in a deregulated environment is proposed. Case studies using the IEEE 14-bus system and the Australian national...

  6. Electricity deregulation roundup : Ontario prepares for electricity deregulation and anxiously watches impact elsewhere

    International Nuclear Information System (INIS)

    Hurst, R.

    2000-01-01

    As the time for deregulation of Ontario's electric power industry approaches, consumers are watching other Canadian and American jurisdictions to see what deregulation will mean in terms of energy costs. Albertans have expressed serious concerns about the impact of deregulating their electric power industry. They found that in the four years since deregulation in their province, electricity prices increased when markets opened to competition. The proposed start date for deregulation in Ontario is November 1, 2000. This paper suggests that if investors don't put out significant resources, problems such as power shortages and brownouts could occur, as was the case in Alberta. Potential investors in the Ontario electricity market are already sceptical because the Ontario government, in an effort to protect consumers from unreasonable price increases, has tabled legislation that restricts the efforts of municipal utility companies to raise distribution rates. One step that will inspire some confidence is the recently finalized deal between Ontario Power Generation and British Energy to operate the Bruce Nuclear Power Station. Independent consultants have warned that electricity prices will continue to increase with deregulation for a least the next few years. Industrial customers will be the hardest hit. In California, America's first deregulated electricity market, the power grid is strained and prices have doubled or tripled in one year

  7. A law enforcement perspective of electricity deregulation

    International Nuclear Information System (INIS)

    Horowitz, Ira

    2006-01-01

    In April 2004, the California Attorney General's (AG) office issued a white paper that provided a 'law enforcement perspective of the California energy crisis.' To complete this special issue's coverage, I summarize three aspects of that paper: notably, the deficiencies in market oversight and enforcement that left the deregulated market prone to potential abuse, the principal modus operandi that some market agents used to exploit those deficiencies without fear of retribution, and the AG's 'recommendations for improving enforcement and protecting consumers in deregulated energy markets.'. (author)

  8. A law enforcement perspective of electricity deregulation

    Energy Technology Data Exchange (ETDEWEB)

    Horowitz, Ira [Warrington College of Business, University of Florida, Gainesville, FL 32611-7169 (United States)

    2006-05-15

    In April 2004, the California Attorney General's (AG) office issued a white paper that provided a 'law enforcement perspective of the California energy crisis.' To complete this special issue's coverage, I summarize three aspects of that paper: notably, the deficiencies in market oversight and enforcement that left the deregulated market prone to potential abuse, the principal modus operandi that some market agents used to exploit those deficiencies without fear of retribution, and the AG's 'recommendations for improving enforcement and protecting consumers in deregulated energy markets.'. (author)

  9. Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

    Science.gov (United States)

    Kowalewski, Ashley A.; Randall, R. Lor; Lessnick, Stephen L.

    2011-01-01

    Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered. PMID:21052502

  10. Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

    Directory of Open Access Journals (Sweden)

    Ashley A. Kowalewski

    2011-01-01

    Full Text Available Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22(q24;q12. This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered.

  11. Complement Activation by Ceramide Transporter Proteins

    NARCIS (Netherlands)

    Bode, G.H.; Losen, M.; Buurman, W.A.; Veerhuis, R.; Molenaar, P.C.; Steinbusch, H.W.M.; De Baets, M.H.; Daha, MR; Martinez-Martinez, P.

    2014-01-01

    C1q is the initiator of the classical complement pathway and, as such, is essential for efficient opsonization and clearance of pathogens, altered self-structures, and apoptotic cells. The ceramide transporter protein (CERT) and its longer splicing isoform CERTL are known to interact with

  12. Genetic Association of the Porcine C9 Complement Component with Hemolytic Complement Activity

    Directory of Open Access Journals (Sweden)

    D. V. A. Khoa

    2015-09-01

    Full Text Available The complement system is a part of the natural immune regulation mechanism against invading pathogens. Complement activation from three different pathways (classical, lectin, and alternative leads to the formation of C5-convertase, an enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in membrane attack complex. The C9 is the last complement component of the terminal lytic pathway, which plays an important role in lysis of the target cells depending on its self-polymerization to form transmembrane channels. To address the association of C9 with traits related to disease resistance, the complete porcine C9 cDNA was comparatively sequenced to detect single nucleotide polymorphisms (SNPs in pigs of the breeds Hampshire (HS, Duroc (DU, Berlin miniature pig (BMP, German Landrace (LR, Pietrain (PIE, and Muong Khuong (Vietnamese potbelly pig. Genotyping was performed in 417 F2 animals of a resource population (DUMI: DU×BMP that were vaccinated with Mycoplasma hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected within the third exon. One of them has an amino acid substitution. The European porcine breeds (LR and PIE show higher allele frequency of these SNPs than Vietnamese porcine breed (MK. Association of the substitution SNP with hemolytic complement activity indicated statistically significant differences between genotypes in the classical pathway but not in the alternative pathway. The interactions between eight time points of measurement of complement activity before and after vaccinations and genotypes were significantly different. The difference in hemolytic complement activity in the both pathways depends on genotype, kind of vaccine, age and the interaction to the other complement components. These results promote the porcine C9 (pC9 as a candidate gene to improve general animal health in the future.

  13. Electricity utility deregulation in Great Britain: economic and industrial consequences

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    In this paper we analyze in the first part how was made the deregulation of the public electric utilities in Great Britain and in the second the logic and the contradictions of this deregulation in an industrial point of view

  14. Industrial consumers and electricity sector deregulation

    International Nuclear Information System (INIS)

    Jukic, A.

    1999-01-01

    The paper presents the electricity sector deregulation from the point of view of major industrial consumers (MIC). Possibilities and limitations of MIC's impact on the introduction and development of an open power market in some European countries, the USA and Croatia are discussed. (author)

  15. IMPACT OF DEREGULATION ON FINANCIAL SECTOR ...

    African Journals Online (AJOL)

    and the efficiency in the allocation of the society's resources, which were not ... financial system so as to make the system operate on the basis of the market ..... cases, the null hypothesis that financial sector deregulation does not granger .... Financial Sector Development and Growth: Evidence from Malaysia, Brookings.

  16. Deregulation of natural gas in Georgia

    International Nuclear Information System (INIS)

    Wise, S.

    2002-01-01

    The Natural Gas Competition and Deregulation Act of 1997 in Georgia is discussed. New legislation passed the Natural Gas Consumer Relief Act in 2002 legislative session to provide additional protection and increase competition. This Act and its impacts are discussed in detail. Additional commission responsibilities are summarized. (R.P.)

  17. Regulatory concern about economic deregulation in Finland

    International Nuclear Information System (INIS)

    Virolainen, R.; Koutaniemi, P.

    2002-01-01

    The deregulation of the electricity market may cause an increased pressure to reduce the costs of electricity generation. This makes a new challenge to the regulatory body to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the economic deregulation. This paper is to discuss the current situation in Finland with regard to the economic deregulation of the electricity market and the experiences so far. A common view today is that the number of electricity generating power companies will be reduced in Europe because of tough competition in the electricity market. It is expected that only the biggest companies can stand the consequences of tough competition in electricity prices and the consequential pressure to reduce costs. In order to review the impact of deregulation of the electricity market some relevant points have been discussed in this paper such as change of ownership of power companies due to the economic pressure, the need to cut costs of the companies by reducing the number of their activities and increasing the efficiency in the remaining activities and/or outsourcing of activities. The need to pursue reduction or delay of planned investments in safety upgrades are discussed as well. (author)

  18. Regulatory concern about economic deregulation in Finland

    International Nuclear Information System (INIS)

    Virolainen, R.; Koutaniemi, P.

    2001-01-01

    The deregulation of the electricity market may cause an increased pressure to reduce the costs of electricity generation. This makes a new challenge to the regulatory body to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the economic deregulation. This paper is to discuss the current situation in Finland with regard to the economic deregulation of the electricity market and the experiences so far. A common view today is that the number of electricity generating power companies will be reduced in Europe because of tough competition in the electricity market. It is expected that only the biggest companies can stand the consequences of tough competition in electricity prices and the consequential pressure to reduce costs. In order to review the impact of deregulation of the electricity market some relevant points have been discussed in this paper, such as change of ownership of power companies due to the economic pressure, the need to cut costs of the companies by reducing the number of their activities and increasing the efficiency in the remaining activities and/or outsourcing of activities. The need to pursue reduction or delay of planned investments in safety upgrades are discussed as well. (author)

  19. Wind power in a deregulated market

    International Nuclear Information System (INIS)

    Ravn, Hans F.

    2000-01-01

    The paper describes organisational and economic elements related to wind power in a deregulated market, it describes physical and technical characteristics of wind power and it describes how wind power is handled in daily operation as well as on the market. (author)

  20. Energy and the deregulated marketplace 1998 survey

    International Nuclear Information System (INIS)

    Fowler, R.B.

    1999-01-01

    In this comprehensive survey of the energy and deregulated marketplace, 911 respondents indicate how deregulation will impact their business. Well organized for easy reference this published survey report provides answers on how companies will procure electricity and natural gas, and what criteria will be used in their decision process. The results presented also illustrate effect of real time pricing on the procurement of energy equipment. Readers will be able to see whether companies are delaying the purchase of energy efficiency equipment as a result of deregulation, as well as what current trends are developing in the use of energy services and performance contracting. The performance and overall cost effectiveness of various types of energy efficient equipment is also rated by respondents, and the results of existing installations is reported. Responses are broken down and can be assessed by respondent categories, including utility, energy supplier, energy user, power marketer, ESCO, equipment supplier, and consultant. This survey report offers a valuable tool for all companies whose business and marketing strategies are impacted by deregulation

  1. Design of reactive power procurement in deregulated electricity market

    African Journals Online (AJOL)

    Reactive power management is different in the deregulated electricity market of various countries. In this paper, a novel reactive power procurement model is proposed, which ensure secure and reliable operation of deregulated electricity market. Various issues of reactive power management in the deregulated electricity ...

  2. Deregulation and competition in the electric utility marketplace

    International Nuclear Information System (INIS)

    Allen, J.E.

    1995-01-01

    This paper addresses the impact of deregulation and competition in the electric utility marketplace as an extension of the deregulation of the airlines, and natural gas, telephone and trucking industries. The topics of the paper include the events and circumstances leading to deregulation, those involved in the competition, and a scenario for how the industry will develop over the next 20 years

  3. Lattices with unique complements

    CERN Document Server

    Saliĭ, V N

    1988-01-01

    The class of uniquely complemented lattices properly contains all Boolean lattices. However, no explicit example of a non-Boolean lattice of this class has been found. In addition, the question of whether this class contains any complete non-Boolean lattices remains unanswered. This book focuses on these classical problems of lattice theory and the various attempts to solve them. Requiring no specialized knowledge, the book is directed at researchers and students interested in general algebra and mathematical logic.

  4. Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H

    1985-01-01

    Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...... of the cellular localization, expression and structure of the C3 receptors, especially the C3b (CR1) receptor, has been considerably extended in the last few years, whereas our understanding of the physiological role of these receptors is still fragmentary. However, it is becoming increasingly evident...

  5. Reactor decommissioning in a deregulated market

    International Nuclear Information System (INIS)

    Beverridge, George; Cooper, T.

    2002-01-01

    Full text: Deregulation of the electricity markets in North America and Western Europe has had many profound effects on the electric utilities and the nuclear industry. Deregulation has led to cost transparency, increased competition, and a drive by the utilities to reduce costs in order to maintain market share and margins. In the context of this more competitive and dynamic market having a clear picture of decommissioning liabilities and their successful discharge has a material impact on the financial performance of a utility. This paper will summarise BNFL Environmental Services' experience with regard to its experience in both the planning and implementation phases of a reactor decommissioning project. In particular it will demonstrate how commercial projects in crucial areas of strategy development, project implementation and site restoration, can be combined with an approach that is both commercial and innovative to reduce the risks to a utility. This paper sets out to demonstrate this viewpoint. (author)

  6. Deregulation of Electricity Supply Industry in Oman

    Directory of Open Access Journals (Sweden)

    Hamed S. Al-Maghderi

    2002-06-01

    Full Text Available This paper examines the opportunities available and the conditions needed for the deregulation of the Electricity Supply Industry (ESI, with particular reference to the Sultanate of Oman. The paper highlights the general issues of regulation required to encourage competition in the ESI.  After that, the discussion focuses on regulation methods in the privatized ESI by describing the regulators control through price caps setting for regulatees, the conduct regulation process, the rate of return regulation setting, and the spot market (the pool contract. Finally, the prospects of restructuring and privatizing the ESI in the Sultanate of Oman are examined by reviewing the current structure of the industry and government objectives in deregulation of the electricity sector as well as the regulation framework.

  7. Utilities' ''obligation to serve'' under deregulation

    International Nuclear Information System (INIS)

    Alexander, C.B.

    1997-01-01

    The utility no longer has protected status, and the traditional franchise concept is under attack. Exclusive rights once conveyed to the utilities are being denied and not just in the area of gas sales. Exclusive rights once conveyed to utilities will be denied in more areas. State by state, the utilities' franchise is being examined to see which, if any, of its provisions are necessary in a deregulated environment. Can the free market provide everything that's been provided for many years under monopolistic arrangements? Some of the most critical and difficult of these provisions concern the obligation to serve, which utilities, in most states, have assumed as part of their franchise agreement. Regulators, courts, utilities, marketers and others are busy sorting through these issues, but resolution could take years. The paper discusses deregulation, universal service fee, representation without taxation, suppliers and marketer restrictions

  8. Gas directive. Which deregulation for France

    International Nuclear Information System (INIS)

    1999-09-01

    This study deals with the following aspects of natural gas market: deregulation of the French market; status and perspectives of the gas market: overview of the gas supplies in Europe at the 2010/2015 vista; situation of regulations: status of the gas directive at the European level and impact on member states market, transposition of the gas directive in France: present day legislation, main stakes and situation of the dialogue with the actors; consequences and actors' strategy: testimony of suppliers, past and future situation, development of new activities in the gas/power industry, possible contractual evolutions, position of the supplier; testimony of clients: new suppliers, new contracts, new risks; legal stakes for the clients: impact of deregulation on contracts, future contractual organization of the market, evolution of 'take or pay' contracts, impairment of contracts obligations, negotiation of supply contracts. (J.S.)

  9. Network industries deregulation and energy industries reorganization

    International Nuclear Information System (INIS)

    Delaporte, P.; Chevalier, J.M.; Bourdaire, J.M.

    1999-01-01

    The electric power distribution systems deregulation is going to change the economical and institutional scenery. The empowerment term can be anything but a happy change for the customer by giving him the free choice. But this evolution calls the public power in question again. Meanwhile the government has to remain vigilant and watch over the safety in terms of cartel and environment risk. (A.L.B.)

  10. Energy subsidies in California's electricity market deregulation

    International Nuclear Information System (INIS)

    Ritschel, Alexander; Smestad, G.P.

    2003-01-01

    Deregulation and re-regulation of California's electricity market not only failed in terms of anticipated cost reductions, improved customer service and higher competition, it also led to the introduction of various additional energy subsidies. This paper analyzes California's electricity market deregulation process from a subsidy viewpoint. Under deregulation in California, investor-owned utilities were not allowed to pass their energy procurement costs fully on to their customers, and therefore subsequently, and inevitably, ran into severe financial problems. Such retail price regulation is an energy subsidy that is both economically and environmentally unfavorable, because it veils true price signals to electricity consumers and, in this way, discourages energy conservation. Other policies implemented in California that represent perverse energy subsidies are the purchase of power by the state of California, the suspension of retail competition, and the potential misuse of money from the recovery of stranded costs. Many interventions implemented by the state to smooth out the impacts of the energy crisis insulated electricity consumers from market realities, supported the existing structure of California's electricity market, which is predominantly based on fossil fuels, and suppressed market incentives to improve energy conservation

  11. Deregulated power prices: comparison of volatility

    International Nuclear Information System (INIS)

    Li Ying; Flynn, P.C.

    2004-01-01

    We examine electrical power price variability for 14 deregulated markets. Power price volatility is measured by price velocity, the daily average of the absolute value of price change per hour. Deregulated markets show a wide variability in price velocity. Some price velocity is expected and arises from the daily diurnal price pattern, which differs significantly between markets. Even when the expected daily variability in price is removed, the residual unexpected variability differs between markets. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent and have low values of unexpected price velocity. These markets create a climate conducive to consumers facing the market through real time pricing and shaping consumption behaviors in response to price changes. Other markets, for example, South Australia and Alberta, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to avoid demand side management and escape risk through hedging mechanisms

  12. Gas and electricity 2000: energy deregulation

    International Nuclear Information System (INIS)

    Hulot, J.C.; Charbit, N.; Tuot, Th.

    2000-11-01

    This document brings together 17 testimonies of experts about the deregulation of the gas and electricity markets. Content: 1 - the new rules controlling the market: schedule and regulatory evolutions, the new legal framework, the new regulation, the missions and competences of the Commission of Electricity Regulation; 2 - the new commercial practices: the question of electricity transport and of the network independence, the development of trading, the stock exchanges and the forecasting of Paris market, the correlations with the environment (eco-taxes and climate change); 3 - the proposals of new actors: the contribution of a deregulated market like Spain, the comparison with a fully open market like Germany, an internal out-sourcing example to create an energy entity as a whole, the role of a bank in the risk management and the derived markets, the contribution of new technologies from service suppliers; 4 - the consumers attitude with respect to new offers: the historical gas and electricity utilities at the service of French and European clients, the new opportunities offered by the deregulation, the contribution of an independent supplier to consumers, the expectations of big companies and eligible consumers. (J.S.)

  13. Complement activation by ceramide transporter proteins.

    Science.gov (United States)

    Bode, Gerard H; Losen, Mario; Buurman, Wim A; Veerhuis, Robert; Molenaar, Peter C; Steinbusch, Harry W M; De Baets, Marc H; Daha, Mohamed R; Martinez-Martinez, Pilar

    2014-02-01

    C1q is the initiator of the classical complement pathway and, as such, is essential for efficient opsonization and clearance of pathogens, altered self-structures, and apoptotic cells. The ceramide transporter protein (CERT) and its longer splicing isoform CERTL are known to interact with extracellular matrix components, such as type IV collagen, and with the innate immune protein serum amyloid P. In this article, we report a novel function of CERT in the innate immune response. Both CERT isoforms, when immobilized, were found to bind the globular head region of C1q and to initiate the classical complement pathway, leading to activation of C4 and C3, as well as generation of the membrane attack complex C5b-9. In addition, C1q was shown to bind to endogenous CERTL on the surface of apoptotic cells. These results demonstrate the role of CERTs in innate immunity, especially in the clearance of apoptotic cells.

  14. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics

    Directory of Open Access Journals (Sweden)

    Francesco Gatto

    2016-07-01

    Full Text Available Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.

  15. Complementing Gender Analysis Methods.

    Science.gov (United States)

    Kumar, Anant

    2016-01-01

    The existing gender analysis frameworks start with a premise that men and women are equal and should be treated equally. These frameworks give emphasis on equal distribution of resources between men and women and believe that this will bring equality which is not always true. Despite equal distribution of resources, women tend to suffer and experience discrimination in many areas of their lives such as the power to control resources within social relationships, and the need for emotional security and reproductive rights within interpersonal relationships. These frameworks believe that patriarchy as an institution plays an important role in women's oppression, exploitation, and it is a barrier in their empowerment and rights. Thus, some think that by ensuring equal distribution of resources and empowering women economically, institutions like patriarchy can be challenged. These frameworks are based on proposed equality principle which puts men and women in competing roles. Thus, the real equality will never be achieved. Contrary to the existing gender analysis frameworks, the Complementing Gender Analysis framework proposed by the author provides a new approach toward gender analysis which not only recognizes the role of economic empowerment and equal distribution of resources but suggests to incorporate the concept and role of social capital, equity, and doing gender in gender analysis which is based on perceived equity principle, putting men and women in complementing roles that may lead to equality. In this article the author reviews the mainstream gender theories in development from the viewpoint of the complementary roles of gender. This alternative view is argued based on existing literature and an anecdote of observations made by the author. While criticizing the equality theory, the author offers equity theory in resolving the gender conflict by using the concept of social and psychological capital.

  16. Deregulated gas in 1985 seen costly

    Energy Technology Data Exchange (ETDEWEB)

    Schaffer, P.

    1980-05-05

    Deregulation of natural gas wellhead prices will mean higher prices for nonboiler industrial users, according to an Energy and Environmental Analysis Inc. (EEA) study. The price increases of high-sulfur residual fuel oil will exceed inflation rates, but low-sulfur residual oil and distillate oil will have smaller increases because of upgraded refineries. Te economc imact analysis is broken down by region and includes estimates of gas, high-sulfur coal, and low-sulfur coal prices thrugh 1995. Free copies of the report are available from the Federal Energy Regulatory Commission's Office of Public Information. (DCK)

  17. Immunological Deregulation in Classic Hodgkin Lymphoma

    Science.gov (United States)

    Romano, Alessandra; Vetro, Calogero; Caocci, Giovanni; Greco, Marianna; Parrinello, Nunziatina Laura; Di Raimondo, Francesco; La Nasa, Giorgio

    2014-01-01

    Classic Hodgkin Lymphoma (cHL) has a unique histology since only a few neoplastic cells are surrounded by inflammatory accessory cells that in the last years have emerged as crucial players in sustaining the course of disease. In addition, recent studies suggest that the abnormal activity of these inflammatory cells (such as deregulation in regulatory T cells signaling, expansion of myeloid derived suppressor cells, HLA-G signaling and natural killer cells dysfunction) may have prognostic significance. This review is focused on summarizing recent advanced in immunological defects in cHL with translational implications. PMID:24959336

  18. Controversies about gas industry deregulation in Europe

    International Nuclear Information System (INIS)

    Percebois, J.

    1992-01-01

    The E.E.C. Commission wishes to introduce more competition into the European gas industry; abolish import public monopolies, resort to competitive bidding for distribution concessions, and to the common carrier system in the transport field. This deregulation policy may induce adverse effects in the long run. This may compromise supply security, and delay the development of new gas fields. This may particularly induce subsidies among users and lead to a reinforcement of regulation if we want the Third Party Access system to respect equality conditions for all users. This paper analyzes arguments for and against this common carrier system. 15 refs., 2 figs

  19. Electric deregulation in Texas : the next steps

    International Nuclear Information System (INIS)

    Giuliani, R.

    2004-01-01

    This presentation provided a look at the deregulated market in Texas and provided some statistics and facts about the Electric Reliability Council of Texas (ERCOT) which monitors the reliability of 37,000 miles of power transmission lines and 77,000 MW of generation. The governance adopted by ERCOT was described along with market design and wholesale operation in terms of open access to transmission and distribution systems, reliability, timely conveyance of information needed to support customer choice, and accurate accountability for electricity production and delivery. Transmission has been one the greatest challenges facing ERCOT, but retail operations are progressing well despite initial start-up problems. tabs., figs

  20. Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

    Science.gov (United States)

    Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

    2013-01-01

    Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

  1. Deregulation, privatization and the Ontario power failure

    International Nuclear Information System (INIS)

    2003-09-01

    The Canadian Union of Public Employees (CUPE) has examined the history of deregulation of the electricity industry in the United States and presents lessons that could be learned from the California electricity crisis, the collapse of Enron, and the massive blackout that occurred in August 2003 across Ontario and northeastern United States. Unlike the United States, Canada's electricity system is mostly publicly owned and operated. This report emphasized that the need for public investment in the electricity system is greater than ever, and offers suggestions on how to strengthen the Canadian electricity system. It examines the attempts made to deregulate and privatize the electricity system in Ontario, Alberta, New Brunswick and British Columbia and exposes the reality of price caps and the debt of public utilities. It demonstrates that privatization has failed to provide a safe, reliable, affordable and adequate supply of electricity. The report claims that profit-seeking power producers want to keep supply and demand in their favour to sell electricity at the highest possible price. In addition to emphasizing the need for public investment in the electricity system, this report emphasizes the need for Canadian electricity cooperation, with particular mention of the large energy supplies in Manitoba and Quebec. 37 refs

  2. Zap... Alberta is jolted by electric deregulation

    International Nuclear Information System (INIS)

    Howe, M.E.

    2001-01-01

    Of all Canadian provinces, Alberta has travelled the furthest along the electric deregulation road. On January 1, 2001, full retail competition came into effect. Wholesale electricity prices are set by the province through an auction process. The bids from purchasers are made through the Power Pool of Alberta against supply offers. Power prices increased from being amongst the lowest in the world to being amongst the highest in North America as a result of deregulation. Changes to the Electric Utilities Act were made recently by the Alberta government to try to mitigate the factors affecting power price increases. RBC Dominion Securities is of the opinion that the changes will not significantly impact the Alberta Pool Price. It is expected that the trend for power price increases to continue, despite some relief from relatively low-cost electricity being felt by other Canadian provinces as a result of the energy crisis in North America. Based on the Electric Competition Unfolds in Alberta report dated June 2, 2001 prepared by RBC Dominion Securities, this document examines the factors at play in electric price increases, assess the sustainability of current power prices in Alberta, and identify Canadian companies believed to be best positioned in the pipeline and gas and electric sectors to benefit from the high power prices in Alberta. Those companies were ATCO, Canadian Utilities, Westcoast Energy and TransCanada PipeLines, and TransAlta. 5 tabs., 5 figs

  3. Selling power : marketing energy under deregulation

    Energy Technology Data Exchange (ETDEWEB)

    Drummond, J.; Hanna, F.

    2001-07-01

    This book discussed the marketing of energy in a deregulated environment. Experience from long distance telephone service providers has shown that historical dominance is not a guarantee for future success. As new brands are introduced and as consumer choice increases, so does the ability to change from one provider to another. Price is only one of the factors prompting that change. Old rules and practices do not bind new competitors who must face the challenge of open competition and must be aware of the ever-changing face of business. It was recommended that the strategic solution would be to build a brand and to develop significant market shares and create effective customer retention programs. This book focused on the elements that energy marketing professionals must use to maintain and increase share without product differentiation. It also explained how energy providers can effectively attract and retain customers over the long term while keeping marketing and service delivery costs down. It was suggested that small players can compete with the growing strength of regional providers by creating new alliances between larger energy conglomerates. The chapters of the book were entitled: (1) Introduction, (2) The Goals of Deregulation, (3) Strategic Marketing Choices, (4) Relationship Marketing, (5) The Role of Customer Service, (6) The Question of Outsourcing, and (7) Final Thoughts and Observations. 24 refs., 3 figs.

  4. Competing in a fully deregulated market

    International Nuclear Information System (INIS)

    Bengtsson, A.; Schoen, G.; Johansson, B.

    1999-01-01

    Vattenfall, Sweden's largest utility, has provided competitively priced nuclear electricity to a price-conscious market for several decades. As Sweden is an exporting country, the cost of products must be kept as low as possible to meet tough European competition. Since Sweden relies almost exclusively on electricity for energy, electric prices must be low to keep Swedish products competitive. Because of the available hydropower in Sweden and Norway, nuclear power plants have been forced to operate with high availability and low cost. From the first years after nuclear plants began operation, there has been a continuous development of organization, management, and work practices to sustain low-cost production. Now, the European electricity market is undergoing deregulation and open competition. This is taking place in a situation where the increase in demand is relatively weak and where the availability of generation capacity is good. Sweden is at the forefront of the competition. According to the well-known law of supply and demand, this entails the risk of squeezed prices, but the situation also offers many opportunities for those making the right decisions. The availability of electricity at competitive prices has great significance for the competitiveness of the industry in general and for the electricity-intensive industry in particular. If the customer then, in a deregulated market is free to choose the supplier, the focus definitely is on the customer

  5. Deregulation : unlocking value : the Australian experience

    International Nuclear Information System (INIS)

    Kwok, F.

    2002-01-01

    Macquarie is a global investment bank based in Australia whose international focus is on niche markets such as infrastructure and utilities. A corporate review of Macquarie is presented along with a review of the evolution of the utility industry from the stages of an integrated utility to fully unbundled entities. In the first stage, the utility is vertically integrated and owned by government, or it is highly regulated. The second stage of evolution involves the unbundling of the utility into separate generation, transmission and distribution companies, each preparing for competition. The third stage involves the introduction of competition to power generation and retail sectors. Transmission and distribution remains regulated in the third stage. The fourth stage involves down-sizing in response to competition and benchmarking. It is also a period of convergence between electricity and gas. The fifth and final stage is for deriving value. Deregulation results in major structural changes and utility managers have to decide how the utility can best deliver value to the shareholders in the new environment. The author discusses how these lessons can be applied to the case of electric power industry deregulation in Alberta

  6. Energy service unbundling: where deregulation is heading

    International Nuclear Information System (INIS)

    Croft, M.

    2002-01-01

    The workings of the natural gas market is provided by the speaker at the beginning of the presentation, and covers pre-regulation, early regulation and deregulation. The pre-regulation era provided no customer choice, and the early regulation period saw industrial customers with some degree of choice (mid-1980s). The advent of deregulation created core market customer choice (around 1996). At Coral Energy, there is choice of energy supplier, choice of price structure, and choice of transportation and distribution. A forecast of North American gas demand is provided, along with the natural gas supply and the North American gas supply basins. For the period January 1996 to May 2000, a comparison of annualized volatility is discussed. The author discusses the strategies for purchasing gas: 1) to know yourself and your risk tolerance, flexibility, and load profile; 2) switching gas supply provider. It is important to choose a three year term, combination pricing, and storage position. The risk management options are reviewed: limit exposure to price volatility, mitigate price/volume volatility, and enhance bottom line by capturing market opportunities. figs

  7. Selling power : marketing energy under deregulation

    International Nuclear Information System (INIS)

    Drummond, J.; Hanna, F.

    2001-01-01

    This book discussed the marketing of energy in a deregulated environment. Experience from long distance telephone service providers has shown that historical dominance is not a guarantee for future success. As new brands are introduced and as consumer choice increases, so does the ability to change from one provider to another. Price is only one of the factors prompting that change. Old rules and practices do not bind new competitors who must face the challenge of open competition and must be aware of the ever-changing face of business. It was recommended that the strategic solution would be to build a brand and to develop significant market shares and create effective customer retention programs. This book focused on the elements that energy marketing professionals must use to maintain and increase share without product differentiation. It also explained how energy providers can effectively attract and retain customers over the long term while keeping marketing and service delivery costs down. It was suggested that small players can compete with the growing strength of regional providers by creating new alliances between larger energy conglomerates. The chapters of the book were entitled: (1) Introduction, (2) The Goals of Deregulation, (3) Strategic Marketing Choices, (4) Relationship Marketing, (5) The Role of Customer Service, (6) The Question of Outsourcing, and (7) Final Thoughts and Observations. 24 refs., 3 figs

  8. Transmission management in the deregulated environment

    International Nuclear Information System (INIS)

    Christie, R.D.; Wollenberg, B.F.; Wangensteen, I.

    2000-01-01

    Three very different methods of accomplishing the same task--managing the operation of the transmission system in the deregulated power system operating environment--have been implemented as deregulated market structures have been created around the world. They are first, the optimal power flow (OPF) model found in various implementations in the United Kingdom, parts of the United States, and in Australia and New Zealand. Second, the point tariff, price area congestion control model used in the Nordpool market area in Norway and Sweden. Third, the US transaction-based model. All are pragmatic solutions implemented in advance of complete theoretical understanding. Each has strengths and flaws, and there are some surprising inter-relationships. Each maintains power system security but differs in its impact on the economics of the energy market. No clearly superior method has so far emerged. In the future, methods of combining decentralized market solutions with operational use of optimal power flow may provide better solutions to existing and emerging problems

  9. Peptide Inhibitor of Complement C1 (PIC1 Rapidly Inhibits Complement Activation after Intravascular Injection in Rats.

    Directory of Open Access Journals (Sweden)

    Julia A Sharp

    Full Text Available The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in pre-clinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1. In this study, we determined that the lead PIC1 variant demonstrates a salt-dependent binding to C1q, the initiator molecule of the classical pathway. Additionally, this peptide bound to the lectin pathway initiator molecule MBL as well as the ficolins H, M and L, suggesting a common mechanism of PIC1 inhibitory activity occurs via binding to the collagen-like tails of these collectin molecules. We further analyzed the effect of arginine and glutamic acid residue substitution on the complement inhibitory activity of our lead derivative in a hemolytic assay and found that the original sequence demonstrated superior inhibitory activity. To improve upon the solubility of the lead derivative, a pegylated, water soluble variant was developed, structurally characterized and demonstrated to inhibit complement activation in mouse plasma, as well as rat, non-human primate and human serum in vitro. After intravenous injection in rats, the pegylated derivative inhibited complement activation in the blood by 90% after 30 seconds, demonstrating extremely rapid function. Additionally, no adverse toxicological effects were observed in limited testing. Together these results show that PIC1 rapidly inhibits classical complement activation in vitro and in vivo and is functional for a variety of animal species, suggesting its utility in animal models of classical complement-mediated diseases.

  10. Nanomedicine and the complement paradigm.

    Science.gov (United States)

    Moghimi, S Moein; Farhangrazi, Z Shadi

    2013-05-01

    The role of complement in idiosyncratic reactions to nanopharmaceutical infusion is receiving increasing attention. We discuss this in relation to nanopharmaceutical development and the possible use of complement inhibitors to prevent related adverse reactions. We further call on initiation of genetic association studies to unravel the genetic basis of nanomedicine infusion-related adverse responses, since most of the polymorphic genes in the genome belong to the immune system. In this paper, idiosyncratic reactions based on complement activation are discussed in the context of newly available complement inhibitors. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Defining the complement biomarker profile of c3 glomerulopathy

    DEFF Research Database (Denmark)

    Zhang, Yuzhou; Nester, Carla M; Martin, Bertha

    2014-01-01

    BACKGROUND AND OBJECTIVES: C3 glomerulopathy (C3G) applies to a group of renal diseases defined by a specific renal biopsy finding: a dominant pattern of C3 fragment deposition on immunofluorescence. The primary pathogenic mechanism involves abnormal control of the alternative complement pathway......, although a full description of the disease spectrum remains to be determined. This study sought to validate and define the association of complement dysregulation with C3G and to determine whether specific complement pathway abnormalities could inform disease definition. DESIGN, SETTING, PARTICIPANTS......, & MEASUREMENTS: This study included 34 patients with C3G (17 with C3 glomerulonephritis [C3GN] and 17 with dense deposit disease [DDD]) diagnosed between 2008 and 2013 selected from the C3G Registry. Control samples (n=100) were recruited from regional blood drives. Nineteen complement biomarkers were assayed...

  12. Systemic complement activation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  13. Deregulation in environmental policy. Aufsaetze zur Wirtschaftspolitik

    Energy Technology Data Exchange (ETDEWEB)

    Orth, J

    1983-01-01

    In the USA the attempt is being made for the first time to leave the solution of the apparent conflict between economy and ecology to a considerable extent to the powers of the market. The framework conditions and rules for that market are characterized by the new approaches of 'deregulation': 'They create a market in which business can make a profit by producing clean air and water.' The aim of the volume is to present that new strategy, with regard to the sector of air pollution, in its individual components, explain their mode of function and briefly indicate associated problems. However, before dealing with the new approaches based on free enterprise, the publication provides some basic information current legislation in the USA regarding air pollution.

  14. Regulatory trends : deregulation, where in the world is it working?

    International Nuclear Information System (INIS)

    Sofield, J.

    2001-01-01

    The issue of electricity deregulation was the focus of this Power-Point presentation, which discussed what deregulation entails, what it is meant to achieve and whether there is only one right answer. Different approaches and performance results were presented with reference to international experiences in the United Kingdom, Australia, New Zealand, and California. The main objective of deregulation is introduce competition to give customers a choice between suppliers and products, to allow market forces to set prices with the hope that they will be lower, and to encourage industry efficiency, reduce costs, improve productivity, and ensure that the right investments are made. The underlying agenda is to raise billions of dollars to reduce government debt and to transfer the risks and investment requirements to the investors and away from the government/taxpayers and ratepayers. Deregulation entails restructuring, privatization and unbundling of monopolies. It also entails a set of market rules and new systems processes to enable retail competition. The author emphasized that there are different characteristics to deregulation in each jurisdiction and that the state of the pre-deregulation industry plays a significant role in the eventual success of deregulation. The lessons learned from international experience is that open, non-discriminatory access is essential for both transmission and distribution and that political will for restructuring is essential. It was also determined that partial deregulation will not work, since wholesale and retail markets are connected. It was concluded that deregulation can work to different degrees under different designs. Progress so far has been slow and customers have yet to see the full benefits of deregulation. tabs

  15. Functional analysis of Ficolin-3 mediated complement activation

    DEFF Research Database (Denmark)

    Hein, Estrid; Honoré, Christian; Skjoedt, Mikkel-Ole

    2010-01-01

    Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA) was acetylated (acBSA) and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation...... was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides...

  16. Deregulation experiences in Alberta and Ontario

    International Nuclear Information System (INIS)

    Axford, D.

    2003-01-01

    A brief introduction of Nexen Chemicals, one of the largest producers of sodium chlorate in the world, was offered, and a map displaying its locations throughout the world was displayed. Nexen is one of Canada's largest independent oil and gas producers, while Nexen Marketing is involved in the marketing of natural gas in North America. In January 2001, the deregulated market opened in Alberta. High natural gas prices, generation shortages, high prices in California and an upcoming provincial election all combined to complicate the situation. A high degree of volatility characterized the market. A chart displaying weekly average Alberta power and gas prices from Jan 2002 to 13 Oct 2002 was shown. In Ontario, the market opened in May 2002, and the demand growth rate was in the 1 to 2 per cent range. The author indicated that approximately 20 per cent of homeowners in Ontario have signed deals with retailers, contrary to Alberta where very few have done so. A similar chart displaying weekly average Ontario power prices was presented. The issues in Ontario are: consistency in policy, increase market transparency, transmission / distribution price flexibility, overall transmission / distribution to industrial consumers high, and increasing costs of the system operator. In Alberta, the issues are: government intent, congestion management issues, and billing settlement errors that continue. The opportunities offered by a deregulated market include process responsiveness which is rewarded, the ability to look in forward prices when prices fit margin requirement, and gives companies the opportunity to participate in the development of the market. Various charts were also displayed to further illustrate the market in both Alberta and Ontario. figs

  17. Complement receptor expression and activation of the complement cascade on B lymphocytes from patients with systemic lupus erythematosus (SLE)

    DEFF Research Database (Denmark)

    Marquart, H V; Svendsen, A; Rasmussen, J M

    1995-01-01

    It has previously been reported that the expression of the complement receptors, CR1 on erythrocytes and blood leucocytes and CR2 on B cells, is reduced in patients with SLE, and that the reduced expression of CR1 on erythrocytes is related to disease activity. We have earlier demonstrated...... that normal B cells are capable of activating the alternative pathway (AP) of complement in a CR2-dependent fashion. In this study we have investigated whether disturbances in this activity may be related to the altered phenotype of SLE B cells. Flow cytometry was used to measure expression of complement...

  18. Determinism and Contingency Shape Metabolic Complementation in an Endosymbiotic Consortium.

    Science.gov (United States)

    Ponce-de-Leon, Miguel; Tamarit, Daniel; Calle-Espinosa, Jorge; Mori, Matteo; Latorre, Amparo; Montero, Francisco; Pereto, Juli

    2017-01-01

    Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism-which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca . Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome-scale metabolic network (GEM) for the bacterial consortium from the cedar aphid i BSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with i BSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is significant in the case of tryptophan biosynthesis, whereas vitamin production pathways seem to adopt suboptimal solutions.

  19. Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3.

    Directory of Open Access Journals (Sweden)

    Michal Potempa

    2009-02-01

    Full Text Available Periodontitis is an inflammatory disease of the supporting structures of the teeth caused by, among other pathogens, Prevotella intermedia. Many strains of P. intermedia are resistant to killing by the human complement system, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with recombinant cysteine protease of P. intermedia (interpain A resulted in a drastic decrease in bactericidal activity of the serum. Furthermore, a clinical strain 59 expressing interpain A was more serum-resistant than another clinical strain 57, which did not express interpain A, as determined by Western blotting. Moreover, in the presence of the cysteine protease inhibitor E64, the killing of strain 59 by human serum was enhanced. Importantly, we found that the majority of P. intermedia strains isolated from chronic and aggressive periodontitis carry and express the interpain A gene. The protective effect of interpain A against serum bactericidal activity was found to be attributable to its ability to inhibit all three complement pathways through the efficient degradation of the alpha-chain of C3 -- the major complement factor common to all three pathways. P. intermedia has been known to co-aggregate with P. gingivalis, which produce gingipains to efficiently degrade complement factors. Here, interpain A was found to have a synergistic effect with gingipains on complement degradation. In addition, interpain A was able to activate the C1 complex in serum, causing deposition of C1q on inert and bacterial surfaces, which may be important at initial stages of infection when local inflammatory reaction may be beneficial for a pathogen. Taken together, the newly characterized interpain A proteinase appears to be an important virulence factor of P. intermedia.

  20. Electric utility deregulation - A nuclear opportunity

    International Nuclear Information System (INIS)

    DeMella, J.R.

    2002-01-01

    The implications of electric deregulation are and will continue to be pervasive and significant. Not only will the fundamental monopoly regulatory concepts of managing electric utilities change but deregulation will have a profound and dramatic impact on the way electric generating plants are managed and operated. In the past, under the various approaches to financial regulation, the economic benefits normally attributed to competition or that would have otherwise been derived from competitive or open market forces, were assumed to be embodied in and inherent to the various processes, methods and principles of financial oversight of utility companies by regional, state and municipal regulatory authorities. Traditionally, under the various forms of regulated monopolies, a utility company, in exchange for an exclusive franchise to produce and sell electricity in a particular region, was obligated to provide an adequate supply to all consumers wanting it, at a price that was 'just and reasonable'. The determination of adequate supply and reasonable price was a matter of interpretation by utility companies and their regulators. In essence, the ultimate economic benefits, normally attributed to price equilibrium, in balance with supply, demand and other market forces, were expected to be achieved through a complex, political process of financial regulatory oversight, in which utility companies were usually reimbursed for all annual expenses or their 'cost of service' and additionally allowed to earn a 'reasonable' rate of return on plant investments. The result was often escalating electric prices, over supplies of electric capacity, by justifying unnecessarily high reserve margins based on long planning horizons (typically 20 years or greater) with extrapolated demand requirements that were generally in excess of what actually occurred over time. Although the regulatory process varied from country or country and region-to-region, the fundamental principles, which

  1. Nuclear communications and deregulated energy market

    International Nuclear Information System (INIS)

    Ruuskanen, Antti

    1998-01-01

    The electricity market a over the world is facing the most profound change ever. The market is to be deregulated, competition will be increased and companies privatised. The boom started from the UK but today the Nordic market is the most liberalised in the world. Nordic market consists of annual power sales around 350 TWh and only a modest growth potential of 12 percent per year. All fuels and all technologies meet in the marketplace. Nuclear has its good one fourth share of the production there. Nuclear is clearly for base-load with low marginal costs next to hydro electric power. There are four major players in the Nordic market. Swedish Vattenfall, IVO Group and Swedish Sydkraft are the three biggest in that order, and all of them have nuclear assets. The market is characterised by lowest power prices in Europe, two electricity exchanges and continuous power trade across the borders. The described market change from national and less open utility driven sector has clear impacts to companies strategies and consequently also to communications. All these circumstances demand, New target groups from corporate communications' point of view; new communications language to change to more business-like; new insider rules and new information practices; new business orientated journalists against a new reference group. This all opens new challenges and possibilities to re-build nuclear image. Market economy in electricity will also ease governmental nationally oriented energy policies and let market forces to decide whether investments are viable or not. This is positive for nuclear - again if and only if the power plants are managed in an economically viable way. Deregulation may open the market from political deadlock to new nuclear investments in case the above mentioned requirements are correct. All in all, market change comes sooner or later to regions not yet liberalised. It will challenge nuclear companies and their communications. The change always creates

  2. Complement in patients receiving maintenance hemodialysis: functional screening and quantitative analysis

    Directory of Open Access Journals (Sweden)

    Horikoshi Satoshi

    2010-12-01

    Full Text Available Abstract Background The complement system is vital for innate immunity and is implicated in the pathogenesis of inflammatory diseases and the mechanism of host defense. Complement deficiencies occasionally cause life-threatening diseases. In hemodialysis (HD patients, profiles on complement functional activity and deficiency are still obscure. The objectives of the present study were to measure the functional complement activities of the classical pathway (CP, lectin pathway (LP and alternative pathway (AP using a novel method and consequently to elucidate the rates of deficiencies among HD patients. Methods In the present study, 244 HD patients at one dialysis center and 204 healthy controls were enrolled. Functional complement activities were measured simultaneously using the Wielisa®-kit. The combination of the results of these three pathway activities allows us to speculate which candidate complement is deficient; subsequently, the deficient complement was determined. Results All three functional complement activities were significantly higher in the HD patients than in the control group (P ®-kit, 16 sera (8.8% with mannose-binding lectin (MBL deficiency, 1 serum (0.4% with C4 deficiency, 1 serum (0.4% with C9 deficiency, and 1 serum (0.4% with B deficiency were observed in the HD group, and 18 sera (8.8% with MBL deficiency and 1 serum (0.5% with B deficiency were observed in the control group. There were no significant differences in the 5-year mortality rate between each complement-deficient group and the complement-sufficient group among the HD patients. Conclusion This is the first report that profiles complement deficiencies by simultaneous measurement of functional activities of the three complement pathways in HD patients. Hemodialysis patients frequently suffer from infections or malignancies, but functional complement deficiencies do not confer additional risk of mortality.

  3. Self-interest, deregulation and trust

    Directory of Open Access Journals (Sweden)

    Salvör Nordal

    2009-11-01

    Full Text Available In this paper I will discuss Milton Friedman’s thesis that the social responsibilityof business is to maximize the shareholders’ profit. I examine the underlyingassumption of self-interest and argue, contrary to the neoliberal thesis ofderegulation, that the profit motive must be constrained by strong state regulations.Furthermore it facilitates keeping the division between business andgovernment intact. The financial crisis shows that the emphasis on a profitmotive without the external constraints of tight regulations has serious implicationsfor the trustworthiness of business. In the latter part of the paper I willdiscuss trust in relation to self-interest. The overemphasis on self-interest isparticularly unfortunate in connection with business, and not least the financialsector, as this institution is grounded in trust, without which it cannot survive.Seen from this angle, it can be claimed that a business model, celebratingprimarily self-interest, profit-motive and deregulation, is not going to be sustainablein the long run.http://dx.doi.org/10.5324/eip.v3i2.1719

  4. The deregulation of Taiwan electricity supply industry

    International Nuclear Information System (INIS)

    Wang, K.M.

    2006-01-01

    Taiwan is on the brink of embarking on an ambitious reform in the electricity sector. The future electricity market of Taiwan will be operated under the framework set out in the Electricity Act Amendment. Independent system operator (ISO) will be the core body of the future market operations and its establishment will therefore be the key to the liberalization. This paper presents the proposed implementation plan based on diverse factors considered by the officials. A three steps phased introduction of Taiwan ISO is discussed. During the proposed Phase I interim market arrangements, Taipower's System Operation Department will assume the role of System Operator for the market. The dispatch rules are largely based on the existing Taipower internal procedure. As competition increases, the need for increased transparency will necessitate the establishment of a fully independent ISO in Phase II to provide the real time dispatch services. This will be completed within 2 years after the passage of the Electricity Act Amendment Bill. In the last phase of the deregulation process a multilateral market arrangement for managing energy imbalance and transmission constraints will result in better outcomes in relation to the policy objectives of security and economic efficiency. The 2-year timeframe stipulated in the Electricity Act Amendment Bill is a challenge for the Government and the industry. However, a smoothly functioning Taiwan ISO will bring benefits to the industry and the country in general

  5. Deregulation and Nuclear Training: Cost Effective Alternatives

    International Nuclear Information System (INIS)

    Richard P. Coe; Patricia A. Lake

    2000-01-01

    Training is crucial to the success of any organization. It is also expensive, with some estimates exceeding $50 billion annually spent on training by U.S. corporations. Nuclear training, like that of many other highly technical organizations, is both crucial and costly. It is unlikely that the amount of training can be significantly reduced. If anything, current trends indicate that training needs will probably increase as the industry and workforce ages and changes. With the advent of energy deregulation in the United States, greater pressures will surface to make the costs of energy more cost-competitive. This in turn will drive businesses to more closely examine existing costs and find ways to do things in a more cost-effective way. The commercial nuclear industry will be no exception, and nuclear training will be equally affected. It is time for nuclear training and indeed the entire nuclear industry to begin using more aggressive techniques to reduce costs. This includes the need for nuclear training to find alternatives to traditional methods for the delivery of cost-effective high-quality training that meets regulatory requirements and produces well-qualified personnel capable of working in an efficient and safe manner. Computer-based and/or Web-based training are leading emerging technologies

  6. Coal marketability: Effects of deregulation and regulation

    International Nuclear Information System (INIS)

    Attanasi, E.

    2000-01-01

    Electrical utility deregulation will force power plants to compete for sales because they will not longer have captive markets. Market uncertainty and uncertainty about future environmental regulations have encouraged power plants to shift to low sulfur coal and/or to use emissions allowances to comply with Phase 2 of the 1990 Clean Air Act Amendments. Mines in Northern and Central Appalachia and the Illinois Basin shipped 240 million tons of non-compliance coal to power plants without scrubbers in 1997. Under Phase 2, this coal will be replaced by low sulfur coal and/or be used with emission permits. It is possible that Powder River Basin coal production will have to increase by over 200 million tons/year to meet new demand. The prices of emissions permits will impose penalties on non-compliance coal that will probably drive out marginal coal producers. For example, if the cost of an emission permit is $200, coal from the Pittsburgh bed could bear a sulfur penalty of $6.55 per ton and similarly, coal from the Herrinbed could bear a penalty of $8.64 per ton

  7. Electricity deregulation - impact on gas users and markets

    International Nuclear Information System (INIS)

    Koeppel, H.

    1995-01-01

    Various scenarios for the natural gas market as a function a electricity deregulation were predicted. One scenario was the formation of an integrated market where sellers would offer a broad spectrum of energy products. This diversification would expand into the retail sector across North America. The second effect of electricity deregulation was energy cost reduction. The consumers have already been experiencing this benefit of deregulation. Cost reduction has also stimulated competition among energy suppliers, and improved suppliers' response to consumers'demands. The eventual shake-out of energy suppliers was predicted. Smaller companies that could not survive the competition would give up the market to larger companies that understood and met the customers' needs. It was concluded that deregulation of the electricity industry would have an enormous impact on the natural gas industry and that there would be opportunities for gain among buyers and sellers

  8. Efficiency and deregulation of the electricity market in Singapore

    International Nuclear Information System (INIS)

    Youngho Chang; Tuan Hin Tay

    2006-01-01

    This study examines production efficiency of electricity generation in the New Electricity Market of Singapore (NEMS), where deregulation is currently proceeding. Singapore is reliant on foreign direct investments and exports so competition from countries with lower costs such as China and India is exerting pressure on the government to reduce the costs of doing business here. Electricity cost is one of these. Deregulation is believed to be able to bring about lower electricity costs due to the various efficiency gains possible. This study concerns itself mainly with production efficiency and attempts to calculate possible production efficiency gains by using linear programming model. Production-efficiency gains are quantified by the base case scenario of continued regulation versus four counterfactual deregulation scenarios. The results indicate that cost gains could be about eight per cent of current production cost, and this is possibly a lower-bound estimate. However, whether the purported efficiency gains are realized is to be seen as the deregulation proceeds. (author)

  9. Efficiency and deregulation of the electricity market in Singapore

    International Nuclear Information System (INIS)

    Chang, Youngho; Hin Tay, Tuan

    2006-01-01

    This study examines production efficiency of electricity generation in the New Electricity Market of Singapore (NEMS), where deregulation is currently proceeding. Singapore is reliant on foreign direct investments and exports so competition from countries with lower costs such as China and India is exerting pressure on the government to reduce the costs of doing business here. Electricity cost is one of these. Deregulation is believed to be able to bring about lower electricity costs due to the various efficiency gains possible. This study concerns itself mainly with production efficiency and attempts to calculate possible production efficiency gains by using linear programming model. Production-efficiency gains are quantified by the base case scenario of continued regulation versus four counterfactual deregulation scenarios. The results indicate that cost gains could be about eight per cent of current production cost, and this is possibly a lower-bound estimate. However, whether the purported efficiency gains are realized is to be seen as the deregulation proceeds

  10. European energy markets deregulation observatory. Winter 2002/2003 period

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    Launched in 2002, the European energy markets deregulation observatory (EEMDO/OELME) aims at actualizing the main energy market indicators and at observing the advance of deregulation within the European countries. While for most of these markets, the deregulation of electricity has preceded the deregulation of gas, the natural gas market is at the evidence a key-market in Europe. For this reason, the 4. edition of the observatory (October 2003) takes into consideration for the first time the specific elements of gas markets, in addition to those of electricity markets. This article presents some excerpts of this last edition, published by Cap Gemini Ernst and Young, and synthesizes the present day situation of gas supplies and the conditions of network access by third parties. The informations reported in the EEMDO come from organizations like UCTE, Nordel, Eurelectric or from energy stock exchanges. (J.S.)

  11. New perspectives on mannan-binding lectin-mediated complement activation

    DEFF Research Database (Denmark)

    Degn, Søren Egedal; Thiel, Steffen; Jensenius, Jens Christian

    2007-01-01

    The complement system is an important part of the innate immune system, mediating several major effector functions and modulating adaptive immune responses. Three complement activation pathways exist: the classical pathway (CP), the alternative pathway (AP), and the lectin pathway (LP). The LP......, allowing C3 activation in the absence of components otherwise believed critical. The classical bypass pathways are dependent on C1 and components of the AP. A recent study has shown the existence also of a lectin bypass pathway dependent on mannan-binding lectin (MBL) and AP components. The emerging...

  12. Deregulation of the electric utility industry - implications for nuclear power

    International Nuclear Information System (INIS)

    Fern, A.Rose

    2000-01-01

    The deregulation movement sweeping the international electric utility community represents a dramatic shift om the traditional business model of utilities. This paper will focus on deregulation in thc United States and the new challenges for nuclear power plant operators. An overview of the new operating models being implemented in the US will lead into a discussion on new economic and operating concerns for nuclear power plant operators. (author)

  13. Deregulation of the electric utility industry - implications for nuclear power

    International Nuclear Information System (INIS)

    Fern, A.R.

    2001-01-01

    The deregulation movement sweeping the international electric utility community represents a dramatic shift from the traditional utility business model. This paper will focus on deregulation in the United States and the new challenges for nuclear power plant operators. An overview of the new operating models being implemented in the US will lead into a discussion on new economic and operating concerns for nuclear power plant operators. (author)

  14. Deregulating the Norwegian railway: a survey of empirical experiences abroad

    OpenAIRE

    Røstadli, Caroline

    2015-01-01

    Portraying implications of deregulation, this thesis presents an extensive review of deregulation in the European railway. It targets various decision variables concerning the introduction of competitive tendering in the rail industry. This thesis attempts to take a pragmatic stand offering an improved understanding vis-à-vis on decisions that have yet to be made, concentrating on possible competition forms, auction designs and contract designs. It offers learning points and tr...

  15. Developing products and services for a deregulated market while regulated

    International Nuclear Information System (INIS)

    Haites, E.F.

    1997-01-01

    Products and services developed for a deregulated electric power industry were discussed. The wide-ranging discussion covered products created by unbundling existing services, new products and services related to energy use, products created by expansion into communications services, and the pricing of products and services. In addition to products and services, the discussion also covered strategies for a deregulated market and the challenges of raising equity capital in a regulated environment

  16. Electricity market deregulation and its impact on the nuclear industry

    International Nuclear Information System (INIS)

    Jung, Y.E.; Alfors, G.

    2000-01-01

    Electricity has traditionally been supplied in OECD countries by state-owned facilities, or state-protected monopolies with regulated pricing. More recently, however, several countries have deregulated their electricity markets, thus opening the door to competitive supply and pricing. Deregulation of electricity markets is a trend that is expected to be followed by many countries, and can have a significant impact on the future of nuclear power programmes. (authors)

  17. Deregulation of the European Banking Industry (1980-1991)

    OpenAIRE

    Gual, Jordi; Neven, Damien J

    1992-01-01

    In this paper the experience of deregulation in the banking sector of seven EC countries (Belgium, France, Germany, Italy, the Netherlands, Spain and the UK) is analysed. Lessons are drawn for assessment of how the EC directives affecting this sector could further affect the industry. Our findings broadly confirm intuition: there is some evidence that firms in protected markets earn large rents, which are partly dissipated in excessive costs and captured by workers. Conduct deregulation seems...

  18. Complement: a key system for immune surveillance and homeostasis.

    Science.gov (United States)

    Ricklin, Daniel; Hajishengallis, George; Yang, Kun; Lambris, John D

    2010-09-01

    Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses and sending 'danger' signals, complement contributes substantially to homeostasis, but it can also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its multiple roles in homeostasis and disease.

  19. Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

    Science.gov (United States)

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

  20. Complement-dependent transport of antigen into B cell follicles

    DEFF Research Database (Denmark)

    Gonzalez, Santiago F.; Lukacs-Kornek, Veronika; Kuligowski, Michael P.

    2010-01-01

    an additional novel pathway in which complement C3 and its receptors enhance humoral immunity through delivery of Ag to the B cell compartment. In this review, we discuss this pathway and highlight several novel exceptions recently found with a model influenza vaccine, such as mannose-binding lectin...... opsonization of influenza and uptake by macrophages, and the capture of virus by dendritic cells residing in the medullary compartment of peripheral lymph nodes....

  1. Complement fixation test to C burnetii

    Science.gov (United States)

    ... complement fixation test; Coxiella burnetii - complement fixation test; C burnetii - complement fixation test ... a specific foreign substance ( antigen ), in this case, C burnetii . Antibodies defend the body against bacteria, viruses, ...

  2. What Drives Deregulation? Economics and Politics of the Relaxation of Bank Branching Restrictions

    OpenAIRE

    Randall S. Kroszner; Philip E. Strahan

    1998-01-01

    This paper examines the key forces behind deregulation in order to assess the relative importance of alternative theories of regulatory entry and exit. We focus on bank branching deregulation across the states which began a quarter century ago and cumulated in federal deregulation in 1994. The cross-sectional and time-series variation of branching deregulation allows us to develop a hazard model to explain the timing of deregulation across the states using proxies motivated by private-interes...

  3. Force Dynamics of Verb Complementation

    Directory of Open Access Journals (Sweden)

    Jacek Woźny

    2015-12-01

    Full Text Available Force Dynamics of Verb Complementation The concepts of motion and force are both extensively discussed in cognitive linguistics literature. But they are discussed separately. The first usually in the context of ‘motion situations’ (Talmy, Slobin, Zlatev, the other as part of the Force Dynamics framework, which was developed by Talmy. The aim of this paper is twofold: first, to argue that the concepts of force and motion should not be isolated but considered as two inseparable parts of force-motion events. The second goal is to prove that the modified Force Dynamics (force-motion framework can be used for precise characterization of the verb complementation patterns. To this end, a random sample of 50 sentences containing the verb ‘went’ is analyzed, demonstrating the differences between the categories of intensive and intransitive complementation with respect to the linguistically coded parameters of force and motion.

  4. Complement: Alive and Kicking Nanomedicines

    DEFF Research Database (Denmark)

    Andersen, Alina Joukainen; Hashemi, S.H.; Andresen, Thomas Lars

    2009-01-01

    Administration of liposome- and polymer-based clinical nanomedicines, as well as many other proposed multifunctional nanoparticles, often triggers hypersensitivity reactions without the involvement of IgE. These anaphylactic reactions are believed to be secondary to activation of the complement...... their procoagulant activity, and has the capacity to elicit non-lytic stimulatory responses from vascular endothelial cells. Here we discuss the molecular basis of complement activation by liposomes, including poly(ethylene glycol) coated vesicles, and other related lipid-based and phospholipid-poly(ethylene glycol...

  5. The undertow of de-regulation : re-regulation

    International Nuclear Information System (INIS)

    Bradford, J.A.

    2003-01-01

    Alberta, Ontario and New Brunswick each initiated steps to deregulate their electric power industries in order to remain competitive with lower electricity rates in certain American states where the industry was also moving towards deregulation. This paper considers how the original sweep of deregulation policy goals succumbed to electricity re regulation policies. The decision by British Columbia to re-examine its deregulation plans in light of the experience in Canada's 3 other province's was also examined. The paper describes the electric power industry from 1900 to 1960s, before the deregulation wave hit the industry and then proceeds to the 1970s which was marked by the oil embargo. The 1980s saw a new era of policy shifts towards deregulation and privatization activity which was intended to introduce competition into regulated industries. Technological advances were taking place in the electricity sector, improving the viability of small gas turbines and making cogeneration possible. In the 1990s, Alberta was the first Canadian province to introduce competition to its electricity industry in an effort to remain competitive with neighbouring U.S. jurisdictions. By the 1990s Ontario's vertically integrated electricity industry was in trouble and recommendations were made to dissolve Ontario's Hydro One monopoly, particularly in power generation. In 1999, New Brunswick restructured its electricity industry to remain competitive with New England's electricity industry. The paper describes the gradual pull back from deregulation by all three provinces and the measures taken to impose price controls. Both industry and consumers paid a price for major policy changes. Complete competition in New Brunswick never materialized. It was suggested that controlled competition will likely move the electricity industry in the future. 40 refs

  6. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

    Directory of Open Access Journals (Sweden)

    Miguel A Brieño-Enríquez

    Full Text Available In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

  7. The Anticomplementary Activity of ’Fusobacterium polymorphum’ in Normal and C-4 Deficient Sources of Guinea Pig Complement.

    Science.gov (United States)

    1977-01-12

    A complement consumption assay was used to show that the anticomplementary activity of a cell wall preparation from F. polymorphum in guinea pig complement...tests with C𔃾-deficient guinea pig sera confirmed that F. polymorphum cell walls were capable of generating alternate complement pathway activity in guinea pig sera.

  8. Complement in the Initiation and Evolution of Rheumatoid Arthritis

    Science.gov (United States)

    Holers, V. Michael; Banda, Nirmal K.

    2018-01-01

    The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA. PMID:29892280

  9. Micrurus snake venoms activate human complement system and generate anaphylatoxins

    Directory of Open Access Journals (Sweden)

    Tanaka Gabriela D

    2012-01-01

    Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

  10. German energy policy in deregulated Europe

    International Nuclear Information System (INIS)

    Kuhnt, D.

    2000-01-01

    The author argues in favor of a more fact-oriented German energy policy: Firstly, German energy policy must accept the new European framework of a market economy. This means that German utilities must no longer be burdened with the implementation of political objectives. The German power industry needs a level playing field for competition on a European scale. Consequently, also the European partner countries should not limit themselves to the minimum conditions of the Single Market Directive in opening their markets. Secondly, German energy policy must develop new forms of cooperation with the power industry so as to maintain domestic employment and the addition of value despite considerably stronger competitive pressure. Also the conflicting targets of sustainability, continuity of supply, and economic viability must not only be discussed, but must be turned into productive approaches. Thirdly, this means that there must be no inadmissible solution in matters nuclear. If the German power industry is to remain strong, in the interest of domestic jobs and opportunities for the future, it must not lose any more domestic market share to other European companies. Fourthly, we need a new energy policy which takes cognizance of the results of market development in a more rational, less emotional way. In this respect, it should be limited henceforth to supporting renewable energies and technologies so as to enhance energy efficiency in line with market requirements. Fifthly, German energy policy must not commit the mistake of enforcing deregulation and, at the same time, exempting large segments of the market from competition. Thus, the planned expansion of renewable energies, and the increase in cogeneration to more than thirty percent of the German electricty generation, by way of quotas and revenues for electricity from these sources fed into the public grid, are incompatible with competition in Europe. The electricity tax within the framework of the eco tax, the

  11. IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study.

    Science.gov (United States)

    Yang, Yang; Wang, Chao; Jin, Liping; He, Fagui; Li, Changchun; Gao, Qingman; Chen, Guanglei; He, Zhijun; Song, Minghui; Zhou, Zhuliang; Shan, Fujun; Qi, Ka; Ma, Lu

    2016-08-01

    The deposition of IgG4 of antibodies against phospholipase A2 receptor (anti-PLA2R) is predominating in the kidneys of patients with idiopathic membranous nephropathy, while its predictive value has not been determined. It was a retrospective study, and 438 patients were included. Serum samples of two time points [before intervention (baseline) and after 1.5-year treatment (endpoint)] were detected for total and IgG4 anti-PLA2R. IgG4 IgG4 subclass and the achievement of CR; (3) bi-negativity of IgG4 has a high accuracy of predicting CR compared with total antibodies; (4) in patients of bi-positivity, those achieving CR showed lower MASP-1/2, MBL, C3a, C5a, FB, Ba and Bb than patients failing to achieve CR; (5) the titers of endpoint and decrease in Ba and Bb were associated with improvement of 24 h-UP in those of bi-positivity; and (6) the decrease in Ba was a significant factor for achieving CR in those of bi-positivity. Continuous IgG4 negativity was a useful tool to predict the achievement of CR; however, in patients of continuous IgG4 positivity, those with lower activation of lectin and alternative pathways would still more probably achieve CR.

  12. Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients

    DEFF Research Database (Denmark)

    Anvar, Seyed Yahya; hoen, Peter Ac; Venema, Andrea

    2011-01-01

    Oculopharyngeal muscular dystrophy (OPMD) is a late-onset progressive muscle disorder caused by a poly-alanine expansion mutation in the Poly(A) Binding Protein Nuclear 1 (PABPN1). The molecular mechanisms that regulate disease onset and progression are largely unknown. In order to identify...... molecular pathways that are consistently associated with OPMD, we performed an integrated high-throughput transcriptome study in affected muscles of OPMD animal models and patients. The ubiquitin-proteasome system (UPS) was found to be the most consistently and significantly OPMD-deregulated pathway across...

  13. Functional analysis of Ficolin-3 mediated complement activation

    DEFF Research Database (Denmark)

    Hein, Estrid; Honoré, Christian Le Fèvre; Skjoedt, Mikkel-Ole

    2010-01-01

    assessed by C4, C3 and terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition...... was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides...

  14. Reincarnation of ancient links between coagulation and complement.

    Science.gov (United States)

    Conway, E M

    2015-06-01

    Throughout evolution, organisms have developed means to contain wounds by simultaneously limiting bleeding and eliminating pathogens and damaged host cells via the recruitment of innate defense mechanisms. Disease emerges when there is unchecked activation of innate immune and/or coagulation responses. A key component of innate immunity is the complement system. Concurrent excess activation of coagulation and complement - two major blood-borne proteolytic pathways - is evident in numerous diseases, including atherosclerosis, diabetes, venous thromboembolic disease, thrombotic microangiopathies, arthritis, cancer, and infectious diseases. Delineating the cross-talk between these two cascades will uncover novel therapeutic insights. © 2015 International Society on Thrombosis and Haemostasis.

  15. Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

    Science.gov (United States)

    Anwar, Sumadi Lukman; Wulaningsih, Wahyu; Lehmann, Ulrich

    2017-01-01

    Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers. PMID:28471386

  16. Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

    Directory of Open Access Journals (Sweden)

    Sumadi Lukman Anwar

    2017-05-01

    Full Text Available Transposable elements (TEs comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers.

  17. Complement-Mediated Enhancement of Monocyte Adhesion to Endothelial Cells by HLA Antibodies, and Blockade by a Specific Inhibitor of the Classical Complement Cascade, TNT003

    Science.gov (United States)

    Valenzuela, Nicole M.; Thomas, Kimberly A.; Mulder, Arend; Parry, Graham C.; Panicker, Sandip; Reed, Elaine F.

    2017-01-01

    Background Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling. Methods Primary human aortic endothelial cells (HAEC) were stimulated with HLA class I antibodies in the presence of intact human serum complement. C3a and C5a generation, endothelial P-selectin expression, and adhesion of human primary and immortalized monocytes (Mono Mac 6) were measured. Alternatively, HAEC or monocytes were directly stimulated with purified C3a or C5a. Classical complement activation was inhibited by pretreatment of complement with an anti-C1s antibody (TNT003). Results Treatment of HAEC with HLA antibody and human complement increased the formation of C3a and C5a. Monocyte recruitment by human HLA antibodies was enhanced in the presence of intact human serum complement or purified C3a or C5a. Specific inhibition of the classical complement pathway using TNT003 or C1q-depleted serum significantly reduced adhesion of monocytes in the presence of human complement. Conclusions Despite persistent endothelial viability in the presence of HLA antibodies and complement, upstream complement anaphylatoxin production exacerbates endothelial exocytosis and leukocyte recruitment. Upstream inhibition of classical complement may be therapeutic to dampen mononuclear cell recruitment and endothelial activation characteristic of microvascular inflammation during AMR. PMID:28640789

  18. Natural gas and deregulation in the European Market

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    The gas market is progressively moving towards new organizations under the effect of deregulation initiated in the United States, the United Kingdom and transposed to other countries, particularly in Europe, at least for the member countries of the European Union. Within the framework provided by this overall trend, Cedigaz proposes a study titled 'Natural Gas and Deregulation' in order to describe the main developments affecting these markets on account of deregulation. This report is structured on the basis of three main topics (market organization, marketing modes, pricing) which appears to be the most cogent in terms of deregulation. This grouping by major topics accordingly offers a relatively synthetic view of the main trends which could be observed in the European market, for example. The analysis is largely based on the example of the American market and, to a lesser extent, on the British situation. Incidentally, it has adapted the terms 'regulated market' to define conventional markets and 'deregulated market' to define markets which have incorporated the principle of Third Party Access (TPA). This is obviously a mere convention, since in both cases, the gas market, a network market, is regulated either by the State or by an independent agency. Also noteworthy is the diversity of the regulation methods for the network markets. While an underlying principle prevails throughout, particularly the introduction of TPA, political and energy considerations alike are liable to condition strongly the final structure of a given market. The apparently comparable British and American experience thus display substantial differences. In other words, one should not imagine a sudden transposition of either case to the European market. The different States preserve considerable leeway to guide market developments in one direction or another. On the whole, deregulation is not a frozen process, but has to adapt permanently to developments in a market stage-managed by

  19. Deregulation of an imprinted gene network in prostate cancer.

    Science.gov (United States)

    Ribarska, Teodora; Goering, Wolfgang; Droop, Johanna; Bastian, Klaus-Marius; Ingenwerth, Marc; Schulz, Wolfgang A

    2014-05-01

    Multiple epigenetic alterations contribute to prostate cancer progression by deregulating gene expression. Epigenetic mechanisms, especially differential DNA methylation at imprinting control regions (termed DMRs), normally ensure the exclusive expression of imprinted genes from one specific parental allele. We therefore wondered to which extent imprinted genes become deregulated in prostate cancer and, if so, whether deregulation is due to altered DNA methylation at DMRs. Therefore, we selected presumptive deregulated imprinted genes from a previously conducted in silico analysis and from the literature and analyzed their expression in prostate cancer tissues by qRT-PCR. We found significantly diminished expression of PLAGL1/ZAC1, MEG3, NDN, CDKN1C, IGF2, and H19, while LIT1 was significantly overexpressed. The PPP1R9A gene, which is imprinted in selected tissues only, was strongly overexpressed, but was expressed biallelically in benign and cancerous prostatic tissues. Expression of many of these genes was strongly correlated, suggesting co-regulation, as in an imprinted gene network (IGN) reported in mice. Deregulation of the network genes also correlated with EZH2 and HOXC6 overexpression. Pyrosequencing analysis of all relevant DMRs revealed generally stable DNA methylation between benign and cancerous prostatic tissues, but frequent hypo- and hyper-methylation was observed at the H19 DMR in both benign and cancerous tissues. Re-expression of the ZAC1 transcription factor induced H19, CDKN1C and IGF2, supporting its function as a nodal regulator of the IGN. Our results indicate that a group of imprinted genes are coordinately deregulated in prostate cancers, independently of DNA methylation changes.

  20. Deregulated microRNAs in CD4+ T cells from individuals with latent tuberculosis versus active tuberculosis.

    Science.gov (United States)

    Fu, Yurong; Yi, Zhengjun; Li, Jianhua; Li, Ruifang

    2014-03-01

    The mechanisms of latent tuberculosis (TB) infection remain elusive. Roles of microRNA (miRNA) have been highlighted in pathogen-host interactions recently. To identify miRNAs involved in the immune response to TB, expression profiles of miRNAs in CD4(+) T cells from patients with latent TB, active TB and healthy controls were investigated by microarray assay and validated by RT-qPCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyse the significant functions and involvement in signalling pathways of the differentially expressed miRNAs. To identify potential target genes for miR-29, interferon-γ (IFN-γ) mRNA expression was measured by RT-qPCR. Our results showed that 27 miRNAs were deregulated among the three groups. RT-qPCR results were generally consistent with the microarray data. We observed an inverse correlation between miR-29 level and IFN-γ mRNA expression in CD4(+) T cells. GO and KEGG pathway analysis showed that the possible target genes of deregulated miRNAs were significantly enriched in mitogen-activated protein kinase signalling pathway, focal adhesion and extracellular matrix receptor interaction, which might be involved in the transition from latent to active TB. In all, for the first time, our study revealed that some miRNAs in CD4(+) T cells were altered in latent and active TB. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in TB. The study might help to improve understanding of the relationship between miRNAs in CD4(+) T cells and TB, and laid an important foundation for further identification of the underlying mechanisms of latent TB infection and its reactivation. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  1. Deregulation, privatisation and marketisation of Nordic comprehensive education

    DEFF Research Database (Denmark)

    Dovemark, Marianne; Kosunen, Sonja; Kauko, Jaakko

    2018-01-01

    economy. The aim of this article is to examine education in the five Nordic countries utilising three dimensions of political change: deregulation, marketisation and privatisation. We also analyse the parallel changes in relation to segregation and differentiation in education. The analysis shows...... that the themes related to deregulation seem to show fairly similar patterns and structures in all contexts. The emerging differences were discovered mainly in the themes of marketisation and privatisation. Institutional segregation emerges in all Nordic countries to different extents along the lines...

  2. Buying and selling green: deregulation and green power marketing

    International Nuclear Information System (INIS)

    Evans, Andrew

    2000-01-01

    This article discusses the increasing trend towards deregulation of electricity markets, and the driving forces for liberalisation in the EU and North America. The use of green tariffs offered by utilities to differentiate themselves from competitors and to gain and keep customers is reported, and the situation with regard to green energy within the deregulated electricity markets in Australia, the EU, Denmark, Finland, Germany, the Netherlands, Portugal, Sweden, the UK, Canada and the USA is outlined. Customers switching as a result of green tariffs, the growing role of renewables, and opportunities for the promotion of green tariffs are discussed. (UK)

  3. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...

  4. Relative Contribution of Cellular Complement Inhibitors CD59, CD46, and CD55 to Parainfluenza Virus 5 Inhibition of Complement-Mediated Neutralization

    Directory of Open Access Journals (Sweden)

    Yujia Li

    2018-04-01

    Full Text Available The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5 incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways. Using a cell line engineered to express CD59, we show that small levels of functional CD59 are associated with progeny PIV5, which is capable of blocking assembly of the C5b-C9 membrane attack complex (MAC. PIV5 containing CD59 (PIV5-CD59 showed increased resistance to complement-mediated neutralization in vitro comparing to PIV5 lacking regulators. Infection of A549 cells with PIV5 and RSV upregulated CD59 expression. TGF-beta treatment of PIV5-infected cells also increased cell surface CD59 expression and progeny virions were more resistant to complement-mediated neutralization. A comparison of individual viruses containing only CD55, CD46, or CD59 showed a potency of inhibiting complement-mediated neutralization, which followed a pattern of CD55 > CD46 > CD59.

  5. 75 FR 68321 - Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready...

    Science.gov (United States)

    2010-11-05

    ...] Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready Alfalfa... Inspection Service has received a supplemental request for ``partial deregulation'' from Forage Genetics... affected persons of the availability of the documents submitted to the Agency from Forage Genetics...

  6. An Agent-based Application to Enable Deregulated Energy Markets

    NARCIS (Netherlands)

    Capodieci, Nicola; Cabri, Giacomo; Pagani, Giuliano Andrea; Aiello, Marco

    2012-01-01

    Private houses are more and more enabled with devices that can produce renewable energy, and the not so remote chance of selling the surplus energy makes them new players in the energy market. This market is likely to become deregulated since each energy home-producer can negotiate the energy price

  7. Gas prices deregulation: how to play the game well?

    International Nuclear Information System (INIS)

    Petitot, Pauline

    2014-01-01

    At the instigation of the European Union and in a context of increasing deregulation, the end of regulated gas prices in France is coming soon. Suppliers and consumers concerned are actively preparing themselves to take the turn of gas market liberalization. This short paper reveals their strategies

  8. Structural Reforms and Growth : Product and Labor Market Deregulations

    NARCIS (Netherlands)

    Eijffinger, S.C.W.; Rossi, A.

    2006-01-01

    The paper focuses on labor and product market deregulations, as fundamental elements in the passage from an investment to an innovation-based economy.The approach undertaken is prominently empirical.After a very brief description of the regulatory levels on the two sides of the Atlantic, we take two

  9. Nuclear regulation on the electrical sector's deregulation horizon

    International Nuclear Information System (INIS)

    Kindelan, J.M.

    1997-01-01

    The electrical sector is generally tending towards a deregulated system which will exert greater pressure on production costs. The author uses this article to reflect on the consequences this new conception will bring for nuclear energy and, particularly, for the activity of regulatory agencies and safety requirements. (Author)

  10. The European gaseous market deregulation and its consequences for Russia

    International Nuclear Information System (INIS)

    Finon, D.; Locatelli, C.

    2002-07-01

    Russia, the first world producer of gas in 2001 is also the main producer in the european gas market. In this framework the evolution of its gas exportations market is a major stake for the russian gas industry and for the country economy. The consequences of this gas market deregulation are analyzed in this document. (A.L.B.)

  11. Deregulation of the Nigerian economy: The theoretical milieu

    Directory of Open Access Journals (Sweden)

    Nureni Opeyemi Akintoye

    2014-01-01

    Full Text Available The deregulation of Nigerian economy was the main thrust of the Structural Adjustment Programme (SAP introduced in the country in 1986 under the leadership of General Ibrahim Babandiga (1958-1993. Prior to that period the Nigerian economy was almost a command one with wide range of government control. Indeed, the introduction of SAP was said to be a final solution to the economic crisis faced by the Country. Unfortunately, SAP was introduced yet, the economy became more crunched. During the General Abach's regime (1993­1998, SAP was suspended out rightly. When General Abdulsalami Abubakar (1998-1999 took over, he continued pursuing the privatization programme which is a synonym of deregulation of the economy with the promulgation of another privatization decree. The civilian government led by President Obasanjo which took over from 1999 made deregulation the core with vigour. It is basked on this development that this paper intends to unravel the theoretical paradigm under which the deregulation of Nigerian economy could be explained. This includes capitalism, imperialism, colonialism particularly the incorporation of Nigerian into international capitalist system.

  12. Deregulation and the Alberta experience : the implications for Ontario

    Energy Technology Data Exchange (ETDEWEB)

    Spearman, C. [Industrial Association of Southern Alberta, Lethbridge, AB (Canada)

    2002-07-01

    The government of Alberta deregulated its electric power industry to introduce industry structure and regulatory reforms that would promote competitive electricity prices. The objective was to ensure fairness for customers and generating facilities. A graph depicting power pool prices shows the reality of soaring prices at the onset of deregulation in Alberta. Today, there remains uncertainty in the development of retail choice, additional rate riders, new generation, transmission expansion, other jurisdictions and future prices. Consumers are still poorly equipped to make decisions and farmers have no means of protection from fluctuating electricity prices. They see deregulation as a complete failure because costs are up and benefits are nowhere to be seen. Ontario can learn from the Alberta experience by adopting the recommendations to set financial penalties for incompetence, financial compensation to customers for errors, and to be fully ready with systems tested ahead of deregulation. Anticipated customer benefits should be clearly identified in advance. The future electric power industry in Ontario needs vision, stability, a cohesive plan, and leadership devoid of complacency. 1 fig.

  13. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Spearman, C.

    2002-01-01

    The government of Alberta deregulated its electric power industry to introduce industry structure and regulatory reforms that would promote competitive electricity prices. The objective was to ensure fairness for customers and generating facilities. A graph depicting power pool prices shows the reality of soaring prices at the onset of deregulation in Alberta. Today, there remains uncertainty in the development of retail choice, additional rate riders, new generation, transmission expansion, other jurisdictions and future prices. Consumers are still poorly equipped to make decisions and farmers have no means of protection from fluctuating electricity prices. They see deregulation as a complete failure because costs are up and benefits are nowhere to be seen. Ontario can learn from the Alberta experience by adopting the recommendations to set financial penalties for incompetence, financial compensation to customers for errors, and to be fully ready with systems tested ahead of deregulation. Anticipated customer benefits should be clearly identified in advance. The future electric power industry in Ontario needs vision, stability, a cohesive plan, and leadership devoid of complacency. 1 fig

  14. Electricity pricing model in thermal generating stations under deregulation

    International Nuclear Information System (INIS)

    Reji, P.; Ashok, S.; Moideenkutty, K.M.

    2007-01-01

    In regulated public utilities with competitive power markets, deregulation has replaced the monopoly. Under the deregulated power market, the electricity price primarily depends on market mechanism and power demand. In this market, generators generally follow marginal pricing. Each generator fixes the electricity price based on their pricing strategy and it leads to more price volatility. This paper proposed a model to determine the electricity price considering all operational constraints of the plant and economic variables that influenced the price, for a thermal generating station under deregulation. The purpose of the model was to assist existing stations, investors in the power sector, regulatory authorities, transmission utilities, and new power generators in decision-making. The model could accommodate price volatility in the market and was based on performance incentive/penalty considering plant load factor, availability of the plant and peak/ off peak demand. The model was applied as a case study to a typical thermal utility in India to determine the electricity price. It was concluded that the case study of a thermal generating station in a deregulated environment showed that the electricity price mainly depended on the gross calorific value (GCV) of fuel, mode of operation, price of the fuel, and operating charges. 11 refs., 2 tabs., 1 fig

  15. Deregulation and restructuring of the electricity sector in Spain

    International Nuclear Information System (INIS)

    Francia, L.

    2000-01-01

    This economic analysis of the Electric Power industry and market in Spain shows how the electricity deregulation and liberalization in Spain have given rise to an electricity industry which not only complies in spirit and letter with the E.U. Directive on the internal energy market, but which in fact goes much further. (A.L.B.)

  16. Vulnerable Consumers in the Deregulated Dutch Health System

    NARCIS (Netherlands)

    Booltink, L.; Genugten, M.L. van; Lako, C.J.

    2015-01-01

    Public service deregulation is favoured for motivating providers to offer consumers better price-quality services. Consequently, consumers are enabled to make informed choices and choose for the best service provider. However, recent publications reveal that consumers are not capable of exercising

  17. Insurance brokers market dynamics in Poland before deregulation

    Directory of Open Access Journals (Sweden)

    Jarosław Krajewski

    2014-12-01

    Full Text Available The article focus on insurance broker profession in connection with second part of professions deregulations. It briefly presents modifications in polish law in this domain. Next part concerns the insurance brokers market dynamics analysis. The results shows permanent increase in brokers quantity in spite of existing regulations. Presented paper makes start point to following analysis.

  18. Nuclear and global warming issues at a deregulated electricity market

    International Nuclear Information System (INIS)

    Mesarovic, M.

    2001-01-01

    The present challenge is to develop such an energy mix that best supports industrial and societal development and improves the quality of life, while simultaneously minimizing health and environmental impacts. Although two decades ago nuclear was considered to be the energy of the future, it is often overlooked in this context and is now even being questioned in many parts of the world. But, for a world facing increased energy demand and growing concerns about global warming due to the emissions of the 'greenhouse' gasses from burning fossil fuels, nuclear power may become the first priority again, since the nuclear power plants proved to be a reliable and safe source of electricity that produce no greenhouse or acid rain gases, and have already demonstrated their economic competitiveness with alternative generating sources of electrical energy. The competitiveness of nuclear power depends essentially on capital investments which must remain low enough to secure its competitive position. However, nuclear electricity in most countries is less competitive than coal and gas, particularly so after deregulation and liberalization of electricity markets have taken place. In the European Union (EU) there are at present 151 reactor blocks and 68 more in the rest of the European continent. Nuclear power plants in EU currently generate about 35% of electricity, but with the new competitive markets, a major decline in the use of coal is compensated for by an increase in gas because of its lower carbon content, and thus almost all new power stations fully or partially use gas as fuel. However, nuclear power is expected to remain a necessary component of the EU's energy mix for the next 20 years and beyond, and in Central and Eastern Europe it is continuing its growth. While Hungary recently gave up plans to construct two more blocks in its 'Pacs' plant, the Czech government agreed to continue construction of two blocks at its 'Temelin' plant. In Rumania, the second unit of

  19. An Oncogenic Role for Alternative NF-κB Signaling in DLBCL Revealed upon Deregulated BCL6 Expression

    Directory of Open Access Journals (Sweden)

    Baochun Zhang

    2015-05-01

    Full Text Available Diffuse large B cell lymphoma (DLBCL is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-κB activity, a role for oncogenic lesions that activate the alternative NF-κB pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-κB pathway, occurs in ∼15% of DLBCLs and that it often coexists with BCL6 translocation, which prevents terminal B cell differentiation. Accordingly, in a mouse model constitutive activation of the alternative NF-κB pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-κB pathway in DLBCL development.

  20. Specificity of EIA immunoassay for complement factor Bb testing.

    Science.gov (United States)

    Pavlov, Igor Y; De Forest, Nikol; Delgado, Julio C

    2011-01-01

    During the alternative complement pathway activation, factor B is cleaved in two fragments, Ba and Bb. Concentration of those fragments is about 2 logs lower than of factor B present in the blood, which makes fragment detection challenging because of potential cross-reactivity. Lack of information on Bb assay cross-reactivity stimulated the authors to investigate this issue. We ran 109 healthy donor EDTA plasmas and 80 sera samples with both factor B immunodiffusion (The Binding Site) and Quidel Bb EIA assays. During the study it was shown that physiological concentrations of gently purified factor B demonstrated approximately 0.15% cross-reactivity in the Quidel Bb EIA assay. We also observed that Bb concentration in serum is higher than in plasma due to complement activation during clot formation which let us use sera as samples representing complement activated state. Our study demonstrated that despite the potential 0.15% cross-reactivity between endogenous factor B and cleaved Bb molecule, measuring plasma concentrations of factor Bb is adequate to evaluate the activation of the alternative complement pathway.

  1. Complements and the Wound Healing Cascade: An Updated Review

    Directory of Open Access Journals (Sweden)

    Hani Sinno

    2013-01-01

    Full Text Available Wound healing is a complex pathway of regulated reactions and cellular infiltrates. The mechanisms at play have been thoroughly studied but there is much still to learn. The health care system in the USA alone spends on average 9 billion dollars annually on treating of wounds. To help reduce patient morbidity and mortality related to abnormal or prolonged skin healing, an updated review and understanding of wound healing is essential. Recent works have helped shape the multistep process in wound healing and introduced various growth factors that can augment this process. The complement cascade has been shown to have a role in inflammation and has only recently been shown to augment wound healing. In this review, we have outlined the biology of wound healing and discussed the use of growth factors and the role of complements in this intricate pathway.

  2. Competitive positioning of power generation plants in a deregulated market

    International Nuclear Information System (INIS)

    Stephens, J.

    1998-01-01

    As industrialized countries deregulate their electric power industries, there is a fundamental shift from guaranteed cost recovery to open market competition on a deregulated grid. Utilities generally competitively bid into a power exchange where the lowest cost power providers are dispatched first. Therefore, the competitiveness of utilities determines their profitability. This commercial structure compels power generators to seek out ways of improving their equipment and plant performance. The inevitability of this trend is demonstrated by a look at the installed base in the US where the move toward deregulation is gaining momentum. More than half of the generating plants in the US are over 20 years old. The average thermal efficiency nation-wide is 33%. In contrast, contemporary coal-and gas-fired plants can operate at efficiency levels up to 45 percent and 55 to 60%, respectfully. With new facilities coming on-line, existing plants will need to make improvements to be dispatched. When deregulation fully envelopes the US market, utilities will not all fit into one pattern; their strategies and actions will depend on a multiple set of factors. Their success will be based on their ability to change landscapes from guaranteed cost recovery to competitive bidding. This paper discussers technical and commercial options available to power producers to improve their competitive positions in a deregulated market as well as software for determining the competitiveness of specific power plants and the location-based market prices of electricity. Examples of the application of alternatives will be cited along with expected payback and impact on cents per kilowatt-hour production costs

  3. Why Shops Close Again : An Evolutionary Perspective on the Deregulation of Shopping Hours

    NARCIS (Netherlands)

    Kosfeld, M.

    1999-01-01

    This paper introduces a new perspective on the deregulation of shopping hours based on ideas from evolutionary game theory. We study a retail economy where shopping hours have been deregulated recently. It is argued that first, the deregulation leads to a coordination problem between store owners

  4. Subversion of complement by hematophagous parasites

    OpenAIRE

    Schroeder, Hélène; Skelly, Patrick; Zipfel, Peter F.; Losson, Bertrand; Vanderplasschen, Alain

    2009-01-01

    The complement system is a crucial part of innate and adaptive immunity which exerts a significant evolutionary pressure on pathogens. It has selected for those pathogens, mainly micro-organisms but also parasites, that have evolved countermeasures. The characterization of how pathogens evade complement attack is a rapidly developing field of current research. In recent years, multiple complement evasion strategies have been characterized. In this review, we focus on complement escape mechani...

  5. conformational complexity of complement component C3

    NARCIS (Netherlands)

    Janssen, B.J.C.

    2007-01-01

    The complement system is an important part of the immune system and critical for the elimination of pathogens. In mammals the complement system consists of an intricate set of about 35 soluble and cell-surface plasma proteins. Central to complement is component C3, a large protein of 1,641 residues.

  6. Complement activation and inhibition: a delicate balance

    DEFF Research Database (Denmark)

    Sjöberg, A P; Trouw, L A; Blom, A M

    2009-01-01

    proteins, pentraxins, amyloid deposits, prions and DNA, all bind the complement activator C1q, but also interact with complement inhibitors C4b-binding protein and factor H. This contrasts to the interaction between C1q and immune complexes, in which case no inhibitors bind, resulting in full complement...

  7. The Complement System: A Prey of Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Kárita C. F. Lidani

    2017-04-01

    Full Text Available Trypanosoma cruzi is a protozoan parasite known to cause Chagas disease (CD, a neglected sickness that affects around 6–8 million people worldwide. Originally, CD was mainly found in Latin America but more recently, it has been spread to countries in North America, Asia, and Europe due the international migration from endemic areas. Thus, at present CD represents an important concern of global public health. Most of individuals that are infected by T. cruzi may remain in asymptomatic form all lifelong, but up to 40% of them will develop cardiomyopathy, digestive mega syndromes, or both. The interaction between the T. cruzi infective forms and host-related immune factors represents a key point for a better understanding of the physiopathology of CD. In this context, the complement, as one of the first line of host defense against infection was shown to play an important role in recognizing T. cruzi metacyclic trypomastigotes and in controlling parasite invasion. The complement consists of at least 35 or more plasma proteins and cell surface receptors/regulators, which can be activated by three pathways: classical (CP, lectin (LP, and alternative (AP. The CP and LP are mainly initiated by immune complexes or pathogen-associated molecular patterns (PAMPs, respectively, whereas AP is spontaneously activated by hydrolysis of C3. Once activated, several relevant complement functions are generated which include opsonization and phagocytosis of particles or microorganisms and cell lysis. An important step during T. cruzi infection is when intracellular trypomastigotes are release to bloodstream where they may be target by complement. Nevertheless, the parasite uses a sequence of events in order to escape from complement-mediated lysis. In fact, several T. cruzi molecules are known to interfere in the initiation of all three pathways and in the assembly of C3 convertase, a key step in the activation of complement. Moreover, T. cruzi promotes secretion

  8. Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis.

    Directory of Open Access Journals (Sweden)

    Nancy A Turner

    Full Text Available Vascular endothelial cells (ECs express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP is an important non-antibody-requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura. Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms.We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs by real-time PCR: C3 and C5; complement factor (CF B, CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not alternative complement pathways. We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of >150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition. We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb on ULVWF strings.AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric strings. Our findings provide one possible molecular mechanism for clinical

  9. Complement Activation in Inflammatory Skin Diseases

    Directory of Open Access Journals (Sweden)

    Jenny Giang

    2018-04-01

    Full Text Available The complement system is a fundamental part of the innate immune system, playing a crucial role in host defense against various pathogens, such as bacteria, viruses, and fungi. Activation of complement results in production of several molecules mediating chemotaxis, opsonization, and mast cell degranulation, which can contribute to the elimination of pathogenic organisms and inflammation. Furthermore, the complement system also has regulating properties in inflammatory and immune responses. Complement activity in diseases is rather complex and may involve both aberrant expression of complement and genetic deficiencies of complement components or regulators. The skin represents an active immune organ with complex interactions between cellular components and various mediators. Complement involvement has been associated with several skin diseases, such as psoriasis, lupus erythematosus, cutaneous vasculitis, urticaria, and bullous dermatoses. Several triggers including auto-antibodies and micro-organisms can activate complement, while on the other hand complement deficiencies can contribute to impaired immune complex clearance, leading to disease. This review provides an overview of the role of complement in inflammatory skin diseases and discusses complement factors as potential new targets for therapeutic intervention.

  10. The long-run price sensitivity dynamics of industrial and residential electricity demand: The impact of deregulating electricity prices

    International Nuclear Information System (INIS)

    Adom, Philip Kofi

    2017-01-01

    This study examines the demand-side of Ghana's electricity sector. We test two important related hypotheses: (1) deregulation of electricity price does not promote energy conservation, and (2) demand-price relationship is not an inverted U-shaped. The Stock and Watson dynamic OLS is used to address the so-called second-order bias. The result showed that, deregulation of electricity price in Ghana has induced behaviours that are more consistent with energy conservation improvements. The demand-price relationship is an inverted U, which suggests that there is a price range that end-users can tolerate further price rise and still increase their consumption of electricity. However, the degree of price tolerability is higher for residential consumers than industrial consumers. The simulation results showed that, further economic growth is likely to compromise energy conservation but more in the industrial sector than the residential sector. On the other hand, future crude oil price is likely to deteriorate energy conservation in the initial years after 2016, but this trend is likely to reverse after the year 2020. Pricing mechanisms are potent to induce energy conservation but inadequate. The results suggest that they should be complemented with other stringent policies such as a mandatory energy reduction policy, investment in renewables, and personalization of energy efficiency programs. - Highlights: • Studies the demand-side of the electricity sector • Deregulating electricity price promotes energy conservation • Demand-price relationship is an inverted U-shaped • Pricing policies should be combined with other energy mandatory reduction policies

  11. The effect of airline deregulation on automobile fatalities.

    Science.gov (United States)

    Bylow, L F; Savage, I

    1991-10-01

    This paper attempts to quantify the effects of airline deregulation in the United States on intercity automobile travel and consequently on the number of highway fatalities. A demand model is constructed for auto travel, which includes variables representing the price and availability of air service. A reduced form model of the airline market is then estimated. Finding that deregulation has decreased airfares and increased flights, it is estimated that auto travel has been reduced by 2.2% per year on average. Given assumptions on the characteristics of drivers switching modes and the types of roads they drove on, the number of automobile fatalities averted since 1978 is estimated to be in the range 200-300 per year.

  12. Economic theory and the failure of electricity deregulation in Sweden

    International Nuclear Information System (INIS)

    Banks, F.E.

    2004-01-01

    The deregulation of electricity has failed in Sweden. Since the beginning of the deregulation 'experiment', the trend price of electricity has increased much faster than the consumer price index, especially during recent years. More importantly, because of (1) the lack of investment in domestic generating (and perhaps transmission) facilities by Swedish power companies, (2) the questionable strategy employed by these firms to mange hydroelectric reserves, (3) increased and to some extent irrational energy taxes, and (4) the beginning of nuclear 'disengagement', households and businesses are vulnerable to a prolonged 'spike' in electricity prices. Everything considered, the recent history of the Swedish electricity sector - and particularly that of the overpraised Nordic Electric Exchange (i.e. Nord Pool) - should be considered a wake-up call instead of an example. (author)

  13. Customer choice: Purchasing energy in a deregulated market

    International Nuclear Information System (INIS)

    Thumann, A.

    1999-01-01

    This book presents the detailed guidance on how to effectively purchase deregulated energy, based on first-hand reports from many of the nation's most knowledgeable experts. It is designed to provide the kind of practical advice needed by professionals who are responsible for making energy purchasing decisions. The book gives a ten-step program to guide building owners in purchasing decision making, a state-by-state retail competition update, and guidelines for buying electricity and natural gas over the worldwide web. Other topics include contract renegotiation strategies, an assessment of power pools, the role of aggregators in the energy market, real time pricing issues, where cogeneration fits within today's marketplace, and lessons learned from deregulation experiences in Scandinavia and England

  14. Revenue opportunities for gas plants arising from electricity deregulation

    International Nuclear Information System (INIS)

    Bachmann, G.C.

    1999-01-01

    A brief overview of deregulation in the electric power industry and an explanation of how these changes can be used to increase revenues of gas processing plants is provided. Deregulation in the electric power industry provides the potential to significantly reduce energy costs for the gas plant and allows technology to be applied to make a better use of a valuable commodity. Owners and operators of gas processing plants increase their operating income by taking advantage of co-generation systems which provide heat and electrical energy to the gas plant. Such an application has three revenue streams, the main one being the power sales to the gas plant, the second one heat sales, and the third increased revenues from the gas plant through a reduction of overall costs, not to mention significantly reduced downtime. Further savings are possible through diversion of excess energy produced to other facilities owned by the gas plant owner

  15. Current issues in Canadian electricity deregulation and competition

    Energy Technology Data Exchange (ETDEWEB)

    Roman, A.J. [Calgary Univ., Calgary, AB (Canada). Canadian Inst. of Resources Law

    1998-03-30

    The deregulation of the electricity industry in Canada was the main focus of this paper. In most developed countries, industries formerly dominated by a monopoly service provider have already been significantly restructured through the introduction of competition. In Canada, such restructuring has taken place only in the airline, railway, natural gas and telephone industry. In most Canadian provinces, except Alberta, electricity generation, transmission and distribution is still owned and operated by provincial and municipal governments. This report examines the present situation in electricity deregulation in Alberta, provides a summary of analysis of London Economics Inc.`s proposals and Bill 27, and presents the author`s own conclusions. A broader perspective and context is provided by references to other regulations of other industries throughout the report.

  16. The role of complement in CD4⁺ T cell homeostasis and effector functions.

    Science.gov (United States)

    Kolev, Martin; Le Friec, Gaëlle; Kemper, Claudia

    2013-02-01

    The complement system is among the evolutionary oldest 'players' of the immune system. It was discovered in 1896 by Jules Bordet as a heat-labile fraction of the serum responsible for the opsonisation and subsequent killing of bacteria. The decades between the 1920s and 1990s then marked the discovery and biochemical characterization of the proteins comprising the complement system. Today, complement is defined as a complex system consisting of more than 30 membrane-bound and soluble plasma proteins, which are activated in a cascade-like manner, very similarly to the caspase proteases and blood coagulation systems. Complement is engrained in the immunologist's mind as a serum-effective, quintessential part of innate immunity, vitally required for the detection and removal of pathogens or other dangerous entities. Three decades ago, this rather confined definition was challenged and then refined when it was shown that complement participates vitally in the induction and regulation of B cell responses, thus adaptive immunity. Similarly, research work published in more recent years supports an equally important role for the complement system in shaping T cell responses. Today, we are again facing paradigm shifts in the field: complement is actively involved in the negative control of T cell effector immune responses, and thus, by definition in immune homeostasis. Further, while serum complement activity is without doubt fundamental in the defence against invading pathogens, local immune cell-derived production of complement emerges as key mediator of complement's impact on adaptive immune responses. And finally, the impact of complement on metabolic pathways and the crosstalk between complement and other immune effector systems is likely more extensive than previously anticipated and is fertile ground for future discoveries. In this review, we will discuss these emerging new roles of complement, with a focus on Th1 cell biology. Copyright © 2013 Elsevier Ltd. All

  17. Price-elastic demand in deregulated electricity markets

    OpenAIRE

    Siddiqui, Afzal S.

    2003-01-01

    The degree to which any deregulated market functions efficiently often depends on the ability of market agents to respond quickly to fluctuating conditions. Many restructured electricity markets, however, experience high prices caused by supply shortages and little demand-side response. We examine the implications for market operations when a risk-averse retailer's end-use consumers are allowed to perceive real-time variations in the electricity spot price. Using a market-equilibrium mo...

  18. Power system restructuring and deregulation: trading, performance and information technology

    International Nuclear Information System (INIS)

    Loi Lei Lai

    2001-09-01

    Representatives from several countries have contributed to a book addressing the deregulation and restructuring of the electric power industry. Articles covered include guidance on asset management, transmission balancing and meter management systems, tools for studying competitive power markets, environmental impacts, costs and benefits, and the new strategies and technology available for power generation, transmission and distribution. The book should be of interest to power systems engineers, system operators, managers, planners and policy makers in the electric power business

  19. Managing an evolution: Deregulation of the electric utility industry

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, S.K.

    1994-12-31

    The author discusses the emerging competitive situation in the electric power industry as deregulation of electric utilities looms on the horizon. The paper supports this change, and the competition it will bring, but urges caution as changes are instituted, and the regulatory bodies decide how and how much to free, and at what rates. The reason for his urge for caution comes from historical experience of other industries, which were smaller and had less direct impact on every American.

  20. Labor market deregulation and globalization: empirical evidence from OECD countries

    OpenAIRE

    Potrafke , Niklas

    2010-01-01

    Abstract This paper empirically investigates the influence of globalization on various aspects of labor market deregulation. I employ the data set by Bassanini and Duval (2006) on labor market institutions in OECD countries and the KOF index of globalization. The data set covers 20 OECD countries in the 1982?2003 period. The results suggest that globalization did neither influence the unemployment replacement rate, the unemployment benefit length, public expenditures on ALMP, the t...

  1. Competitive nuclear production on the nordic deregulated electricity market

    International Nuclear Information System (INIS)

    Bohl, T.

    2000-01-01

    The Nordic electricity market has been partly deregulated since 1994. Today only Denmark follows the timetable recommended by the European Union, while Sweden, Norway and Finland are completely deregulated. As in most countries, the production of electricity is deregulated while the distribution is still a monopoly. This deregulation of the electricity market has created a new situation for plant life management. In order to be competitive on the market it is important to cut cost down a level when the nuclear power companies earn money again. All means to cut cost have to be used while still maintaining safety and the possibilities for operation over at least 40+ years. The possibilities to invest in modernization are limited to the absolutely necessary modifications. All investments must be very thoroughly questioned and the money can only be spent where most benefit is gained. This means new prerequisites for the absolute necessary long-strategic planning. New safety requirements from the authorities have to be discussed between the industry and the authority. The requirement cost must be compared to the benefit to safety. The authority is today requested to carry out such analyses and do so in most cases. Since the electricity market is international the requirements of the authorities must be harmonized on the whole market. The political threat against nuclear power is serious in many countries and it is important to continue working with public acceptance and lobbying. Especially in Sweden a lot of effort is spent on trying to change the taxation of nuclear power. In the near future increasing electricity demand will make the prices go up to a level when nuclear power companies earn money again. The very serious worries about climate change will also strengthen the competitiveness of nuclear power. (author)

  2. Generation capacity expansion planning in deregulated electricity markets

    Science.gov (United States)

    Sharma, Deepak

    With increasing demand of electric power in the context of deregulated electricity markets, a good strategic planning for the growth of the power system is critical for our tomorrow. There is a need to build new resources in the form of generation plants and transmission lines while considering the effects of these new resources on power system operations, market economics and the long-term dynamics of the economy. In deregulation, the exercise of generation planning has undergone a paradigm shift. The first stage of generation planning is now undertaken by the individual investors. These investors see investments in generation capacity as an increasing business opportunity because of the increasing market prices. Therefore, the main objective of such a planning exercise, carried out by individual investors, is typically that of long-term profit maximization. This thesis presents some modeling frameworks for generation capacity expansion planning applicable to independent investor firms in the context of power industry deregulation. These modeling frameworks include various technical and financing issues within the process of power system planning. The proposed modeling frameworks consider the long-term decision making process of investor firms, the discrete nature of generation capacity addition and incorporates transmission network modeling. Studies have been carried out to examine the impact of the optimal investment plans on transmission network loadings in the long-run by integrating the generation capacity expansion planning framework within a modified IEEE 30-bus transmission system network. The work assesses the importance of arriving at an optimal IRR at which the firm's profit maximization objective attains an extremum value. The mathematical model is further improved to incorporate binary variables while considering discrete unit sizes, and subsequently to include the detailed transmission network representation. The proposed models are novel in the

  3. Hepatitis C virus NS3/4A protease inhibits complement activation by cleaving complement component 4.

    Directory of Open Access Journals (Sweden)

    Seiichi Mawatari

    Full Text Available BACKGROUND: It has been hypothesized that persistent hepatitis C virus (HCV infection is mediated in part by viral proteins that abrogate the host immune response, including the complement system, but the precise mechanisms are not well understood. We investigated whether HCV proteins are involved in the fragmentation of complement component 4 (C4, composed of subunits C4α, C4β, and C4γ, and the role of HCV proteins in complement activation. METHODS: Human C4 was incubated with HCV nonstructural (NS 3/4A protease, core, or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then subjected to peptide sequencing. The activity of the classical complement pathway was examined using an erythrocyte hemolysis assay. The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells, respectively, was also examined. RESULTS: HCV NS3/4A protease cleaved C4γ in a concentration-dependent manner, but viral core and NS5 did not. A specific inhibitor of NS3/4A protease reduced C4γ cleavage. NS3/4A protease-mediated cleavage of C4 inhibited classical pathway activation, which was abrogated by a NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild-type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4γ fragments. Such C4 processing, with a concomitant reduction in levels of full-length C4γ, was also observed in HCV-infected cells expressing C4. CONCLUSIONS: C4 is a novel cellular substrate of the HCV NS3/4A protease. Understanding disturbances in the complement system mediated by NS3/4A protease may provide new insights into the mechanisms underlying persistent HCV infection.

  4. Accounting for gas in a de-regulated environment

    International Nuclear Information System (INIS)

    Zawalykut, P.M.

    1992-01-01

    Since the natural gas industry was deregulated, the method of buying, selling and moving gas has changed significantly. Post-deregulation, the pipeline company moves the gas but does not acquire ownership. The full impact of deregulation is seen in opening up the market for buying and selling gas. Tracking of gas has become critical. The service customer is now buying and moving gas. The end-use customer nominates to the distribution company a quantity of gas to be transported. Responsibility is placed on the customer to estimate loads as accurately as possible to avoid possible charges. The distribution company passes the end-user nomination to the upstream transmission company, which in turn passes it along, a process that is repeated until the nomination reaches the production company. Authorizations for gas follow a similar path. The major difference between sales and service gas is the accounting and tracking. As the customer will not consume the exact amount nominated, there will be an imblance between what was nominated and metered. There will also be imbalances between what the producer places into the pipeline and what was nominated. These processes can cause administrative problems, and many customers are moving from sales to service

  5. Analysis of deregulation models; Denryoku shijo jiyuka model no bunseki

    Energy Technology Data Exchange (ETDEWEB)

    Yajima, M. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1996-04-01

    Trends toward power market deregulation were investigated in Japan and 16 other countries, and various deregulation models were examined and evaluated for their merits and demerits. There are four basic models, that is, franchise bidding model, competitive bidding in power generation model, wholesale wheeling or retail wheeling model, and mandatory pool or voluntary pool model. Power market deregulation has been a global tendency since the second half of the 1970s, with various models adopted by different countries. Out of the above-said models, it is the retail wheeling model and pool models (open access models) that allow the final customer to select power suppliers, and the number of countries adopting these models is increasing. The said models are characterized in that the disintegration of the vertical transmission-distribution integration (separation of distribution service and retail supply service) and the liberation of the retail market are simultaneously accomplished. The pool models, in particular, are enjoying favor because conditions for fair competition have already been prepared and because it is believed high in efficiency. In Japan and France, where importance is attached to atomic power generation, the competitive bidding model is adopted as a means to harmonize the introduction of competition into the source development and power generation sectors. 7 refs., 4 tabs.

  6. Inflow shortages in deregulated power markets - Reasons for concern?

    Energy Technology Data Exchange (ETDEWEB)

    Bye, Torstein; Bruvoll, Annegrete; Aune, Finn Roar [Research Department, Statistics Norway, P.O. Box 8131 Dep., 0033 Oslo (Norway)

    2008-07-15

    In many countries hydropower constitutes a large share of the electricity producing capacity. In the earlier regulated electricity markets, production capacities exceeded demand due to security of supply concerns. The present deregulated markets base investments upon profitability alone, and security of supply issues are claimed to be less important. Market operators trust the pricing mechanism in competitive markets to clear. Then low inflow constitutes a less problem. Several markets, both under regulated and deregulated regimes, have faced serious droughts. Some of them have experienced problems with market clearance (Chile, Brazil, California) while other markets functioned well (The Nordic market). Important features to the market response are the flexibility of demand, the pattern of inflow shortage, the storage capacities, the possibility of trade between regions with different production technologies, and the market design and concentration. We apply an empirical based market model to simulate the effects under two inflow shortage scenarios in an international market with combined hydro and thermal capacities and restricted transmission capacities. We compare the scenarios with actual events and show that the model and the real market outcome are comparable. The simulations do not reveal any problems with the functioning of the market, which should calm down the anxiousness about security of supply in deregulated markets with stochastic energy supply. (author)

  7. Inflow shortages in deregulated power markets - Reasons for concern?

    International Nuclear Information System (INIS)

    Bye, Torstein; Bruvoll, Annegrete; Aune, Finn Roar

    2008-01-01

    In many countries hydropower constitutes a large share of the electricity producing capacity. In the earlier regulated electricity markets, production capacities exceeded demand due to security of supply concerns. The present deregulated markets base investments upon profitability alone, and security of supply issues are claimed to be less important. Market operators trust the pricing mechanism in competitive markets to clear. Then low inflow constitutes a less problem. Several markets, both under regulated and deregulated regimes, have faced serious droughts. Some of them have experienced problems with market clearance (Chile, Brazil, California) while other markets functioned well (The Nordic market). Important features to the market response are the flexibility of demand, the pattern of inflow shortage, the storage capacities, the possibility of trade between regions with different production technologies, and the market design and concentration. We apply an empirical based market model to simulate the effects under two inflow shortage scenarios in an international market with combined hydro and thermal capacities and restricted transmission capacities. We compare the scenarios with actual events and show that the model and the real market outcome are comparable. The simulations do not reveal any problems with the functioning of the market, which should calm down the anxiousness about security of supply in deregulated markets with stochastic energy supply

  8. Retail experience in the de-regulated market

    International Nuclear Information System (INIS)

    Cummings, R.

    2003-01-01

    This paper describes the experience gained to date in the de-regulated electricity market through an examination of the commercial market. In 2001, chaos provided opportunity, while in 2002 the emphasis was on operations. In 2003, the landscape reflected hyper-competition, selling second services, and a changing landscape. A discussion followed on the residential market with a look at market structure, economics, and uncertainty concerning the future. The following components were identified as working well: wholesale market, commercial market, market model/data, and innovation in offerings and green supply. Areas requiring further improvement were also identified. It was suggested that the residential de-regulated roadmap should be clarified and retail friendly transactions should be imposed. Other improvements involve education and operations/system capabilities. The author concluded that the deregulated electricity market is still an immature market, where progress is being made in the commercial market. The residential market is in a critical period, with a market model still evolving. figs

  9. Cycles in deregulated electricity markets: Empirical evidence from two decades

    International Nuclear Information System (INIS)

    Arango, Santiago; Larsen, Erik

    2011-01-01

    In this article, we discuss the 'cycle hypothesis' in electricity generation, which states that the introduction of deregulation in an electricity system might lead to sustained fluctuations of over- and under-capacity. The occurrence of cycles is one of the major threats for electricity markets as it affects the security of supply, and creates uncertainty in both the profitability of electricity companies and in consumer prices. We discuss the background for these cycles using analogies with other capital-intensive industries, along with evidence from the analysis of behavioral simulation models as well as from experimental electricity markets. Using data from the oldest deregulated markets we find support for the hypothesis in the case of the English and Chilean markets, based on an autocorrelation analysis. Evidence from the Nordpool market is more ambiguous, although we might be observing the first half of a cycle in generation capacity. Comparing a simulation of the English market performed in 1992 with the actual performance we can observe that the qualitative behavior of the model is consistent with the actual evolution. Finally, we discuss possible mechanisms for damping cycles in electricity generation, such as mothballing, capacity payments, and reliability markets. - Research highlights: → We explore the emergence of cycles in the electricity generation capacity after deregulation. → We discuss the reason for cycles in generation capacity and compare different theories. → Analysis of England and Chile data show strong indications that cycles have emerged.

  10. Choice of electricity provider in California after deregulation

    Science.gov (United States)

    Keanini, Rasa Ilze

    Surveys often ask consumers how much they are willing to pay for certain goods and services, without requiring the consumer to actually pay for the good or service. Such surveys, termed stated preference studies, find that consumers value renewable electricity. This result is in contrast to actual experiences in recently deregulated electricity markets in several states, including California. When given the opportunity to choose in California, only one to two percent of the population opted for renewable electricity products. This dissertation used data from residential customers who chose an alternative electricity product in California's deregulated electricity market to determine the value placed on the renewable attribute of electricity products. This dissertation begins by taking a historical look at the electricity market of the nation and specifically California. From 1998 through 2001, California's electricity market was deregulated to include retail competition. This dissertation used data from electric service providers to reveal the factors influencing residential customer's choice of electricity product. Discrete choice models were used to determine the factors influencing electricity product choice. The results indicated that both price and renewable content had an effect on choice of product. Additionally, a more complicated model jointly estimating the discrete choice of electricity product with the continuous choice of electricity consumption (kWh) was specified and estimated.

  11. Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Ng, O H; Erbilgin, Y; Firtina, S; Celkan, T; Karakas, Z; Aydogan, G; Turkkan, E; Yildirmak, Y; Timur, C; Zengin, E; Dongen, J J M van; Staal, F J T; Ozbek, U; Sayitoglu, M

    2014-01-01

    WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated β-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When β-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL

  12. Complement activation in emergency department patients with severe sepsis.

    Science.gov (United States)

    Younger, John G; Bracho, David O; Chung-Esaki, Hangyul M; Lee, Moonseok; Rana, Gurpreet K; Sen, Ananda; Jones, Alan E

    2010-04-01

    This study assessed the extent and mechanism of complement activation in community-acquired sepsis at presentation to the emergency department (ED) and following 24 hours of quantitative resuscitation. A prospective pilot study of patients with severe sepsis and healthy controls was conducted among individuals presenting to a tertiary care ED. Resuscitation, including antibiotics and therapies to normalize central venous and mean arterial pressure (MAP) and central venous oxygenation, was performed on all patients. Serum levels of Factor Bb (alternative pathway), C4d (classical and mannose-binding lectin [MBL] pathway), C3, C3a, and C5a were determined at presentation and 24 hours later among patients. Twenty patients and 10 healthy volunteer controls were enrolled. Compared to volunteers, all proteins measured were abnormally higher among septic patients (C4d 3.5-fold; Factor Bb 6.1-fold; C3 0.8-fold; C3a 11.6-fold; C5a 1.8-fold). Elevations in C5a were most strongly correlated with alternative pathway activation. Surprisingly, a slight but significant inverse relationship between illness severity (by sequential organ failure assessment [SOFA] score) and C5a levels at presentation was noted. Twenty-four hours of structured resuscitation did not, on average, affect any of the mediators studied. Patients with community-acquired sepsis have extensive complement activation, particularly of the alternative pathway, at the time of presentation that was not significantly reversed by 24 hours of aggressive resuscitation.

  13. Dynamics of human complement-mediated killing of Klebsiella pneumoniae.

    Science.gov (United States)

    Nypaver, Christina M; Thornton, Margaret M; Yin, Suellen M; Bracho, David O; Nelson, Patrick W; Jones, Alan E; Bortz, David M; Younger, John G

    2010-11-01

    With an in vitro system that used a luminescent strain of Klebsiella pneumoniae to assess bacterial metabolic activity in near-real-time, we investigated the dynamics of complement-mediated attack in healthy individuals and in patients presenting to the emergency department with community-acquired severe sepsis. A novel mathematical/statistical model was developed to simplify light output trajectories over time into two fitted parameters, the rate of complement activation and the delay from activation to the onset of killing. Using Factor B-depleted serum, the alternative pathway was found to be the primary bactericidal effector: In the absence of B, C3 opsonization as measured by flow cytometry did not progress and bacteria proliferated near exponentially. Defects in bacterial killing were easily demonstrable in patients with severe sepsis compared with healthy volunteers. In most patients with sepsis, the rate of activation was higher than in normal subjects but was associated with a prolonged delay between activation and bacterial killing (P < 0.05 for both). Theoretical modeling suggested that this combination of accentuated but delayed function should allow successful bacterial killing but with significantly greater complement activation. The use of luminescent bacteria allowed for the development of a novel and powerful tool for assessing complement immunology for the purposes of mechanistic study and patient evaluation.

  14. Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

    Science.gov (United States)

    Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

    2016-01-01

    To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

  15. Complement and hyper acute rejection

    Directory of Open Access Journals (Sweden)

    Al-Rabia Mohammed

    2009-01-01

    Full Text Available Organ transplantation has been a major development in clinical medicine but its success has been marred by the immune system′s capacity to respond to "non-self" cells and tissues. A full molecular understanding of this mechanism and the myriad triggers for immune rejection is yet to be elucidated. Consequently, immunosuppressive drugs remain the mainstay of post-transplant ma-nagement; however, these interventions have side effects such as increased incidence of cancer, post-transplant lymphoproliferative disorders, susceptibility to infection if not managed appro-priately and the inconvenience to the patient of lifelong treatment. Novel therapeutic approaches based on molecular understanding of immunological processes are thus needed in this field. The notion that factors influencing successful transplants might be of use as therapeutic approaches is both scientifically and medically appealing. Recent developments in the understanding of successful transplants are expected to provide new opportunities for safer transplantation. This article reviews the present understanding of the molecular basis of rejection and the role of complement in this process as well as the possibility of generating "intelligent" therapy that better target crucial components of hyper-acute rejections.

  16. Subversion of complement by hematophagous parasites.

    Science.gov (United States)

    Schroeder, Hélène; Skelly, Patrick J; Zipfel, Peter F; Losson, Bertrand; Vanderplasschen, Alain

    2009-01-01

    The complement system is a crucial part of innate and adaptive immunity which exerts a significant evolutionary pressure on pathogens. It has selected for those pathogens, mainly microorganisms but also parasites, that have evolved countermeasures. The characterization of how pathogens evade complement attack is a rapidly developing field of current research. In recent years, multiple complement evasion strategies have been characterized. In this review, we focus on complement escape mechanisms expressed by hematophagous parasites, a heterogeneous group of metazoan parasites that share the property of ingesting the whole blood of their host. Complement inhibition is crucial for parasite survival within the host tissue or to facilitate blood feeding. Finally, complement inhibition by hematophagous parasites may also contribute to their success as pathogen vectors.

  17. Novel roles of complement in renal diseases and their therapeutic consequences.

    Science.gov (United States)

    Wada, Takehiko; Nangaku, Masaomi

    2013-09-01

    The complement system functions as a part of the innate immune system. Inappropriate activation of the complement pathways has a deleterious effect on kidneys. Recent advances in complement research have provided new insights into the pathogenesis of glomerular and tubulointerstitial injury associated with complement activation. A new disease entity termed 'C3 glomerulopathy' has recently been proposed and is characterized by isolated C3 deposition in glomeruli without positive staining for immunoglobulins. Genetic and functional studies have demonstrated that several different mutations and disease variants, as well as the generation of autoantibodies, are potentially associated with its pathogenesis. The data from comprehensive analyses suggest that complement dysregulation can also be associated with hemolytic uremic syndrome and more common glomerular diseases, such as IgA nephropathy and diabetic kidney disease. In addition, animal studies utilizing genetically modified mice have begun to elucidate the molecular pathomechanisms associated with the complement system. From a diagnostic point of view, a noninvasive, MRI-based method for detecting C3 has recently been developed to serve as a novel tool for diagnosing complement-mediated kidney diseases. While novel therapeutic tools related to complement regulation are emerging, studies evaluating the precise roles of the complement system in kidney diseases will still be useful for developing new therapeutic approaches.

  18. Deregulation strategies for local governments and the role/opportunities for energy efficiency services in the utility industry deregulation

    International Nuclear Information System (INIS)

    Tseng, P.C.

    1998-01-01

    As the future shape of the electric utility industry continues to unfold and as retail competition becomes a reality, local governments are faced with balancing the need for: (1) economic development; (2) and to avoid the potential impact of cost-shifting among residents and businesses, while ensuring reliable and universal energy services. Furthermore, local governments need to find ways to recoup potential loss of franchise and tax revenues, to ensure fair and adequate energy-efficiency programs, and to continue other social programs for low income families. This paper will address two important issues every local government in the US are facing: (1) the development of viable deregulation strategies before, during and after the promulgation of utility deregulation; (2) opportunities for energy efficiency services in the competitive markets to serve local governments, which typically constitutes the largest market segment in utility's service territory. This paper presents issues and challenges common to all local governments. It documents strategies that several local governments are utilizing to embrace the coming electric utility restructuring and competition challenge to the benefits of their respective communities. This paper presents the results on deregulation work by the City of Portland, Oregon, Barnstable County, Massachusetts, and Montgomery County, Maryland. The research by these local governments was sponsored by the Urban Consortium Energy Task Force and Public Technology, Inc

  19. Deregulation strategies for local governments and the role/opportunities for energy efficiency services in the utility industry deregulation

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, P.C.

    1998-07-01

    As the future shape of the electric utility industry continues to unfold and as retail competition becomes a reality, local governments are faced with balancing the need for: (1) economic development; (2) and to avoid the potential impact of cost-shifting among residents and businesses, while ensuring reliable and universal energy services. Furthermore, local governments need to find ways to recoup potential loss of franchise and tax revenues, to ensure fair and adequate energy-efficiency programs, and to continue other social programs for low income families. This paper will address two important issues every local government in the US are facing: (1) the development of viable deregulation strategies before, during and after the promulgation of utility deregulation; (2) opportunities for energy efficiency services in the competitive markets to serve local governments, which typically constitutes the largest market segment in utility's service territory. This paper presents issues and challenges common to all local governments. It documents strategies that several local governments are utilizing to embrace the coming electric utility restructuring and competition challenge to the benefits of their respective communities. This paper presents the results on deregulation work by the City of Portland, Oregon, Barnstable County, Massachusetts, and Montgomery County, Maryland. The research by these local governments was sponsored by the Urban Consortium Energy Task Force and Public Technology, Inc.

  20. A study on the deregulation of the Finnish electricity markets

    International Nuclear Information System (INIS)

    Kopsakangas-Savolainen, M.

    2002-01-01

    Governments have regarded the electricity industry as a leading industrial sector throughout the history. Because of its strategic importance to industrial development, its impacts on the social and environmental issues and its natural monopoly characteristics, it has been seen necessary to regulate electricity industry effectively. However, in the mid 1980s it was realised that even though transmission and distribution networks are natural monopolies, the scale economies in electricity production at the generating unit level had exhausted at a unit size of about 500 MW. This meant that supply and generation had become potentially competitive activities. In Finland the new Electricity Market Act (EMA) came into force in 1.11.1995. According to it the production and supply of electricity became deregulated and competition was introduced to the industry. The main aim of the law was to improve efficiency. This dissertation analyses, both theoretically and empirically, the impacts of deregulation to the Finnish electricity markets. In chapter two we discuss on the grounds and incentives of the deregulation processes that have been carried out in different countries. We also determine the crucial factors in order succeed in the deregulation process. According to our view the success depend on the number of active players in the wholesale market, the rules of the bidding procedure, the organisation of the demand side operation, the neutrality of transmission grid, the structure of production technologies and the ownership structure of the industry. In chapter three we theoretically model the profit maximising behaviour of the Finnish electricity companies based on different stages of vertical integration and on different stage of competition. According to our results the profit maximising pricing rules of distribution units is dependent on the stage of integration and on the stage of competition. The separated distribution company maximises profits by setting the

  1. Pasteurella pneumotropica evades the human complement system by acquisition of the complement regulators factor H and C4BP.

    Directory of Open Access Journals (Sweden)

    Alfredo Sahagún-Ruiz

    Full Text Available Pasteurella pneumotropica is an opportunist Gram negative bacterium responsible for rodent pasteurellosis that affects upper respiratory, reproductive and digestive tracts of mammals. In animal care facilities the presence of P. pneumotropica causes severe to lethal infection in immunodeficient mice, being also a potential source for human contamination. Indeed, occupational exposure is one of the main causes of human infection by P. pneumotropica. The clinical presentation of the disease includes subcutaneous abscesses, respiratory tract colonization and systemic infections. Given the ability of P. pneumotropica to fully disseminate in the organism, it is quite relevant to study the role of the complement system to control the infection as well as the possible evasion mechanisms involved in bacterial survival. Here, we show for the first time that P. pneumotropica is able to survive the bactericidal activity of the human complement system. We observed that host regulatory complement C4BP and Factor H bind to the surface of P. pneumotropica, controlling the activation pathways regulating the formation and maintenance of C3-convertases. These results show that P. pneumotropica has evolved mechanisms to evade the human complement system that may increase the efficiency by which this pathogen is able to gain access to and colonize inner tissues where it may cause severe infections.

  2. Complement anaphylatoxins as immune regulators in cancer

    OpenAIRE

    Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

    2014-01-01

    The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediat...

  3. Complement anaphylatoxins as immune regulators in cancer.

    Science.gov (United States)

    Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

    2014-08-01

    The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediated suppression of immune effector cells responsible for immunosurveillance within the tumor microenvironment. This paradigm accords with models of immune dysregulation, such as autoimmunity and infectious disease, which have defined a pathophysiological role for abnormal complement signaling. Several types of immune cells express the cognate receptors for the complement anaphylatoxins, C3aR and C5aR, and demonstrate functional modulation in response to complement stimulation. In turn, impairment of antitumor immunity has been intimately tied to tumor progression in animal models of cancer. In this article, the literature was systematically reviewed to identify studies that have characterized the effects of the complement anaphylatoxins on the composition and function of immune cells within the tumor microenvironment. The search identified six studies based upon models of lymphoma and ovarian, cervical, lung, breast, and mammary cancer, which collectively support the paradigm of complement as an immune regulator in the tumor microenvironment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. A tick mannose-binding lectin inhibits the vertebrate complement cascade to enhance transmission of the Lyme disease agent

    OpenAIRE

    Schuijt, Tim J.; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; DePonte, Kathleen; Wouters, Diana; Brouwer, Mieke; Oei, Anneke; Roelofs, Joris J.T.H.; van Dam, Alje P.; van der Poll, Tom; van ’t Veer, Cornelis; Hovius, Joppe W.; Fikrig, Erol

    2011-01-01

    The Lyme disease agent, Borrelia burgdorferi, is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8 that reduced complement-mediated killing of Borrelia. We now discover that P8 interferes with the human lectin complement cascade resulting in impaired neutrophil phagocytosis and chemotaxis, and diminished Borrelia lysi...

  5. Controlling the complement system in inflammation.

    Science.gov (United States)

    Kirschfink, M

    1997-12-01

    Inappropriate or excessive activation of the complement system can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. These consequences are clinically manifested in various disorders, including septic shock, multiple organ failure and hyperacute graft rejection. Genetic complement deficiencies or complement depletion have been proven to be beneficial in reducing tissue injury in a number of animal models of severe complement-dependent inflammation. It is therefore believed that therapeutic inhibition of complement is likely to arrest the process of certain diseases. Attempts to efficiently inhibit complement include the application of endogenous soluble complement inhibitors (C1-inhibitor, recombinant soluble complement receptor 1- rsCR1), the administration of antibodies, either blocking key proteins of the cascade reaction (e.g. C3, C5), neutralizing the action of the complement-derived anaphylatoxin C5a, or interfering with complement receptor 3 (CR3, CD18/11b)-mediated adhesion of inflammatory cells to the vascular endothelium. In addition, incorporation of membrane-bound complement regulators (DAF-CD55, MCP-CD46, CD59) has become possible by transfection of the correspondent cDNA into xenogeneic cells. Thereby, protection against complement-mediated inflammatory tissue damage could be achieved in various animal models of sepsis, myocardial as well as intestinal ischemia/reperfusion injury, adult respiratory distress syndrome, nephritis and graft rejection. Supported by results from first clinical trials, complement inhibition appears to be a suitable therapeutic approach to control inflammation. Current strategies to specifically inhibit complement in inflammation have been discussed at a recent meeting on the 'Immune Consequences of Trauma, Shock and Sepsis', held from March 4-8, 1997, in Munich, Germany. The Congress (chairman: E. Faist, Munich, Germany), which was held in close cooperation with various

  6. Complement is activated in progressive multiple sclerosis cortical grey matter lesions.

    Science.gov (United States)

    Watkins, Lewis M; Neal, James W; Loveless, Sam; Michailidou, Iliana; Ramaglia, Valeria; Rees, Mark I; Reynolds, Richard; Robertson, Neil P; Morgan, B Paul; Howell, Owain W

    2016-06-22

    The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression. We analysed complement expression and activation by immunocytochemistry and in situ hybridisation in frozen or formalin-fixed paraffin-embedded post-mortem tissue blocks from 22 progressive MS cases and made comparisons to inflammatory central nervous system disease and non-neurological disease controls. Expression of the transcript for C1qA was noted in neurons and the activation fragment and opsonin C3b-labelled neurons and glia in the MS cortical and deep grey matter. The density of immunostained cells positive for the classical complement pathway protein C1q and the alternative complement pathway activation fragment Bb was significantly increased in cortical grey matter lesions in comparison to control grey matter. The number of cells immunostained for the membrane attack complex was elevated in cortical lesions, indicating complement activation to completion. The numbers of classical (C1-inhibitor) and alternative (factor H) pathway regulator-positive cells were unchanged between MS and controls, whilst complement anaphylatoxin receptor-bearing microglia in the MS cortex were found closely apposed to cortical neurons. Complement immunopositive neurons displayed an altered nuclear morphology, indicative of cell stress/damage, supporting our finding of significant neurodegeneration in cortical grey matter lesions. Complement is activated in the MS cortical grey matter lesions in areas of elevated numbers of complement receptor-positive microglia and suggests that complement over-activation may contribute to the worsening pathology that underlies the

  7. Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease.

    Science.gov (United States)

    Pandey, Manoj K; Burrow, Thomas A; Rani, Reena; Martin, Lisa J; Witte, David; Setchell, Kenneth D; Mckay, Mary A; Magnusen, Albert F; Zhang, Wujuan; Liou, Benjamin; Köhl, Jörg; Grabowski, Gregory A

    2017-03-02

    Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease. Marked local and systemic complement activation occurred in GCase-deficient mice or after pharmacological inhibition of GCase and was associated with GC storage, tissue inflammation and proinflammatory cytokine production. Whereas all GCase-inhibited mice died within 4-5 weeks, mice deficient in both GCase and C5aR1, and wild-type mice in which GCase and C5aR were pharmacologically inhibited, were protected from these adverse effects and consequently survived. In mice and humans, GCase deficiency was associated with strong formation of complement-activating GC-specific IgG autoantibodies, leading to complement activation and C5a generation. Subsequent C5aR1 activation controlled UDP-glucose ceramide glucosyltransferase production, thereby tipping the balance between GC formation and degradation. Thus, extensive GC storage induces complement-activating IgG autoantibodies that drive a pathway of C5a generation and C5aR1 activation that fuels a cycle of cellular GC accumulation, innate and adaptive immune cell recruitment and activation in Gaucher disease. As enzyme replacement and substrate reduction therapies are expensive and still associated with inflammation, increased risk of cancer and Parkinson disease, targeting C5aR1 may serve as a treatment option for patients with Gaucher disease and, possibly, other lysosomal storage diseases.

  8. Complement factor H deficiency and endocapillary glomerulonephritis due to paternal isodisomy and a novel factor H mutation

    DEFF Research Database (Denmark)

    Schejbel, L; Schmidt, I M; Kirchhoff, Eva Maria

    2011-01-01

    Complement factor H (CFH) is a regulator of the alternative complement activation pathway. Mutations in the CFH gene are associated with atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II and C3 glomerulonephritis. Here, we report a 6-month-old CFH-deficient child...

  9. Reactivity of alpha 1-antitrypsin mutants against proteolytic enzymes of the kallikrein-kinin, complement, and fibrinolytic systems

    NARCIS (Netherlands)

    Patston, P.A.; Roodi, N.; Schifferli, J.A.; Bischoff, Rainer; Courtney, M.; Schapira, M.

    1990-01-01

    Increased extracellular proteolysis because of unregulated activation of blood coagulation, complement, and fibrinolysis is observed in thrombosis, shock, and inflammation. In the present study, we have examined whether the plasma kallikrein-kinin system, the classical pathway of complement, and the

  10. Interactions of the humoral pattern recognition molecule PTX3 with the complement system

    DEFF Research Database (Denmark)

    Doni, Andrea; Garlanda, Cecilia; Bottazzi, Barbara

    2012-01-01

    The innate immune system comprises a cellular and a humoral arm. The long pentraxin PTX3 is a fluid phase pattern recognition molecule, which acts as an essential component of the humoral arm of innate immunity. PTX3 has antibody-like properties including interactions with complement components....... PTX3 interacts with C1q, ficolin-1 and ficolin-2 as well as mannose-binding lectin, recognition molecules in the classical and lectin complement pathways. The formation of these heterocomplexes results in cooperative pathogen recognition and complement activation. Interactions with C4b binding protein...

  11. Protective function of complement against alcohol-induced rat liver damage.

    Science.gov (United States)

    Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

    2004-11-01

    The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

  12. Complement elevation in spinal cord injury.

    Science.gov (United States)

    Rebhun, J; Botvin, J

    1980-05-01

    Laboratory studies revealed an elevated complement in 66% of patients with spinal cord injury. It is postulated that the activated complement may be a component of self-feeding immunological mechanism responsible for the failure of regeneration of a mature mammalian spinal cord. There was no evidence that such an injury had any effect on pre-existing atopy.

  13. Noun complement clauses as referential modifiers

    Directory of Open Access Journals (Sweden)

    Carlos de Cuba

    2017-01-01

    Full Text Available A number of recent analyses propose that so-called noun complement clauses should be analyzed as a type of relative clause. In this paper, I present a number of complications for any analysis that equates noun complement clauses to relative clauses, and conclude that this type of analysis is on the wrong track. I present cross-linguistic evidence showing that the syntactic behavior of noun complement clauses does not pattern with relative clauses. Patterns of complementizer choice and complementizer drop as well as patterns involving main clause phenomena and extraction differ in the two constructions, which I argue is unexpected under a relative clause analysis that involves operator movement. Instead I present an alternative analysis in which I propose that the referentiality of a noun complement clause is linked to its syntactic behavior. Following recent work, I claim that referential clauses have a syntactically truncated left-periphery, and this truncation can account for the lack of main clause phenomena in noun complement clauses. I argue that the truncation analysis is also able to accommodate complementizer data patterns more easily than relative clause analyses that appeal to operator movement.

  14. Viral mimicry of the complement system

    Indian Academy of Sciences (India)

    The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign pathogens. Although viruses are smaller in size and have relatively simple structure, they are not immune to complement attack. Thus, activation of the ...

  15. Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Pauline E Jullien

    2010-03-01

    Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

  16. ‘N-of-1-pathways’ unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: towards precision medicine

    Science.gov (United States)

    Gardeux, Vincent; Achour, Ikbel; Li, Jianrong; Maienschein-Cline, Mark; Li, Haiquan; Pesce, Lorenzo; Parinandi, Gurunadh; Bahroos, Neil; Winn, Robert; Foster, Ian; Garcia, Joe G N; Lussier, Yves A

    2014-01-01

    Background The emergence of precision medicine allowed the incorporation of individual molecular data into patient care. Indeed, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery. Method ‘N-of-1-pathways’ is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity between genesets/biomodules assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1-pathways predicts the deregulated pathways of each patient. Results Cross-patient N-of-1-pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations. Moreover, heatmap and star plots highlight both individual and shared mechanisms ranging from molecular to organ-systems levels (eg, DNA repair, signaling, immune response). Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03). Conclusions The N-of-1-pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies. It enables mechanism-level classifiers with smaller cohorts as well as N-of-1 studies. Software http://lussierlab.org/publications/N-of-1-pathways

  17. Bank CEO Pay-Performance Relations and the Effects of Deregulation.

    OpenAIRE

    Crawford, Anthony J; Ezzell, John R; Miles, James A

    1995-01-01

    The authors test the deregulation hypothesis that posits that bank CEO compensation became more sensitive to performance as bank management became less regulated. They observe a significant increase in pay-performance sensitivities from their 1976-81 regulation subsample to their 1982-88 deregulation subsample. These increases in pay sensitivities after deregulation are observed for salary and bonus, stock options, and common stock holdings. The authors observe increases in the pay-performanc...

  18. Product Market Deregulation and Employment Outcomes: Evidence from the German Retail Sector

    OpenAIRE

    Charlotte Senftleben-König

    2014-01-01

    This paper investigates the short- and medium-term effects of the deregulation of shopopening hours legislation on retail employment in Germany. In 2006, the legislative competence was shifted from the federal to the state level, leading to a gradual deregulation of shop opening restrictions in most of Germany’s sixteen federal states. The paper exploits regional variation in the legislation in order to identify the effect product market deregulation has on retail employment. We find robust...

  19. Why Shops Close Again : An Evolutionary Perspective on the Deregulation of Shopping Hours

    OpenAIRE

    Kosfeld, M.

    1999-01-01

    This paper introduces a new perspective on the deregulation of shopping hours based on ideas from evolutionary game theory. We study a retail economy where shopping hours have been deregulated recently. It is argued that first, the deregulation leads to a coordination problem between store owners and customers, and second, the ‘solution’ to this problem depends on the specific cost structure of stores and the preferences of customers. In particular, it may happen that, even if extended shoppi...

  20. The German Political Economy Between Deregulation and Re-regulation: Party Discourses on Minimum Wage Policies

    OpenAIRE

    Dostal, Jörg Michael

    2012-01-01

    In the German political economy of the early 21st century, labor market policymaking has shifted toward deregulation and liberalization. In particular, the so-called Hartz labor market reforms of the Social Democratic Party and Green Party government, introduced in 2002 and 2003, pushed for employment growth in low-wage and deregulated employment sectors. This article focuses on one of the key debates triggered by Germany’s labor market deregulation after 2002, namely whethe...

  1. Human pentraxin 3 binds to the complement regulator c4b-binding protein.

    Directory of Open Access Journals (Sweden)

    Anne Braunschweig

    Full Text Available The long pentraxin 3 (PTX3 is a soluble recognition molecule with multiple functions including innate immune defense against certain microbes and the clearance of apoptotic cells. PTX3 interacts with recognition molecules of the classical and lectin complement pathways and thus initiates complement activation. In addition, binding of PTX3 to the alternative complement pathway regulator factor H was shown. Here, we show that PTX3 binds to the classical and lectin pathway regulator C4b-binding protein (C4BP. A PTX3-binding site was identified within short consensus repeats 1-3 of the C4BP α-chain. PTX3 did not interfere with the cofactor activity of C4BP in the fluid phase and C4BP maintained its complement regulatory activity when bound to PTX3 on surfaces. While C4BP and factor H did not compete for PTX3 binding, the interaction of C4BP with PTX3 was inhibited by C1q and by L-ficolin. PTX3 bound to human fibroblast- and endothelial cell-derived extracellular matrices and recruited functionally active C4BP to these surfaces. Whereas PTX3 enhanced the activation of the classical/lectin pathway and caused enhanced C3 deposition on extracellular matrix, deposition of terminal pathway components and the generation of the inflammatory mediator C5a were not increased. Furthermore, PTX3 enhanced the binding of C4BP to late apoptotic cells, which resulted in an increased rate of inactivation of cell surface bound C4b and a reduction in the deposition of C5b-9. Thus, in addition to complement activators, PTX3 interacts with complement inhibitors including C4BP. This balanced interaction on extracellular matrix and on apoptotic cells may prevent excessive local complement activation that would otherwise lead to inflammation and host tissue damage.

  2. Targeting Apoptosis Signaling Pathways for Anticancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fulda, Simone, E-mail: simone.fulda@kgu.de [Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt (Germany)

    2011-08-29

    Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

  3. Targeting Apoptosis Signaling Pathways for Anticancer Therapy

    International Nuclear Information System (INIS)

    Fulda, Simone

    2011-01-01

    Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

  4. Crosstalk between Complement and Toll-like Receptor Activation in Relation to Donor Brain Death and Renal Ischemia-Reperfusion Injury

    NARCIS (Netherlands)

    Damman, Jeffrey; Daha, Mohamed R.; van Son, Willem J.; Leuvenink, Henri G.; Ploeg, Rutger J.; Seelen, Marc A.

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen

  5. Power systems locational marginal pricing in deregulated markets

    Science.gov (United States)

    Wang, Hui-Fung Francis

    Since the beginning of the 1990s, the electricity business is transforming from a vertical integrating business to a competitive market operations. The generation, transmission, distribution subsystem of an electricity utility are operated independently as Genco (generation subsystem), Transco (transmission subsystem), and Distco (distribution subsystem). This trend promotes more economical inter- and intra regional transactions to be made by the participating companies and the users of electricity to achieve the intended objectives of deregulation. There are various types of electricity markets that are implemented in the North America in the past few years. However, transmission congestion management becomes a key issue in the electricity market design as more bilateral transactions are traded across long distances competing for scarce transmission resources. It directly alters the traditional concept of energy pricing and impacts the bottom line, revenue and cost of electricity, of both suppliers and buyers. In this research, transmission congestion problem in a deregulated market environment is elucidated by implementing by the Locational Marginal Pricing (LMP) method. With a comprehensive understanding of the LMP method, new mathematical tools will aid electric utilities in exploring new business opportunities are developed and presented in this dissertation. The dissertation focuses on the development of concept of (LMP) forecasting and its implication to the market participants in deregulated market. Specifically, we explore methods of developing fast LMP calculation techniques that are differ from existing LMPs. We also explore and document the usefulness of the proposed LMP in determining electricity pricing of a large scale power system. The developed mathematical tools use of well-known optimization techniques such as linear programming that are support by several flow charts. The fast and practical security constrained unit commitment methods are the

  6. Deregulation and pricing in a hydro electric system

    International Nuclear Information System (INIS)

    Stoea, P.; Livik, K.; Wangensteen, I.

    1992-01-01

    In line with the current development in some European countries, notably the UK and the Netherlands, deregulation and market competition has been introduced in Norwegian electricity supply in order to improve the economic efficiency of the system. The legal basis for the introduction is the new Norwegian Energy Act that was approved in the Storting (parliament) in June 1990 and came legally into effect on January 1, 1991. This paper deals with the organizational structure, the price formation in the wholesale market, and the tariffs and metering equipment that are being developed to meet the needs of the customers and the utilities in this new situation. (author)

  7. A congestion line flow control in deregulated power system

    Directory of Open Access Journals (Sweden)

    Venkatarajan Shanmuga Sundaram

    2011-01-01

    Full Text Available Under open access, market-driven transactions have become the new independent decision variables defining the behavior of the power system. The possibility of transmission lines getting over-loaded is relatively more under deregulated operation because different parts of the system are owned by separate companies and in part operated under varying service charges. This paper discusses a two-tier algorithm for correcting the lone overloads in conjunction with the conventional power-flow methods. The method uses line flow sensitivities, which are computed by the East Decoupled Power-flow algorithm and can be adapted for on-line implementation.

  8. Complement activation by Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, E T; Kharazmi, A; Garred, P

    1993-01-01

    In chronic infections, such as the bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients, bacteria persist despite an intact host immune defense and frequent antibiotic treatment. An important reason for the persistence of the bacteria is their capacity for the biofilm...... mode of growth. In this study we investigated the role of biofilms in activation of complement, a major contributor to the inflammatory process. Complement activation by P. aeruginosa was examined in a complement consumption assay, production of C3 and factor B conversion products assessed by crossed...... immuno-electrophoresis, C5a generation tested by a PMN chemotactic assay, and terminal complement complex formation measured by ELISA. Two of the four assays showed that P. aeruginosa grown in biofilm activated complement less than planktonic bacteria, and all assays showed that activation by intact...

  9. M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.

    Science.gov (United States)

    Bahia El Idrissi, Nawal; Das, Pranab K; Fluiter, Kees; Rosa, Patricia S; Vreijling, Jeroen; Troost, Dirk; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

    2015-05-01

    Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.

  10. The regulation and deregulation of Wnt signaling by PARK genes in health and disease.

    Science.gov (United States)

    Berwick, Daniel C; Harvey, Kirsten

    2014-02-01

    Wingless/Int (Wnt) signaling pathways are signal transduction mechanisms that have been widely studied in the field of embryogenesis. Recent work has established a critical role for these pathways in brain development, especially of midbrain dopaminergic neurones. However, the fundamental importance of Wnt signaling for the normal function of mature neurones in the adult central nervous system has also lately been demonstrated by an increasing number of studies. Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide and is currently incurable. This debilitating disease is characterized by the progressive loss of a subset of midbrain dopaminergic neurones in the substantia nigra leading to typical extrapyramidal motor symptoms. The aetiology of PD is poorly understood but work performed over the last two decades has identified a growing number of genetic defects that underlie this condition. Here we review a growing body of data connecting genes implicated in PD--most notably the PARK genes--with Wnt signaling. These observations provide clues to the normal function of these proteins in healthy neurones and suggest that deregulated Wnt signaling might be a frequent pathomechanism leading to PD. These observations have implications for the pathogenesis and treatment of neurodegenerative diseases in general.

  11. Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma.

    Science.gov (United States)

    Roos, Frederik C; Evans, Andrew J; Brenner, Walburgis; Wondergem, Bill; Klomp, Jeffery; Heir, Pardeep; Roche, Olga; Thomas, Christian; Schimmel, Heiko; Furge, Kyle A; Teh, Bin T; Thüroff, Joachim W; Hampel, Christian; Ohh, Michael

    2011-02-01

    Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. The Nightmare of the Leader: The Impact of Deregulation on an Oligopoly Insurance Market

    OpenAIRE

    Jennifer L. Wang; Larry Y. Tzeng; En-Lin Wang

    2003-01-01

    This paper explores the impact of deregulation of licensing on an oligopoly insurance market. We show that deregulation of licensing in a Stackelberg-type oligopoly market may not have any impact on the leader’s output if the number of firms increases but the market structure remains. On the other hand, if the market structure is reorganized because of the deregulation of licensing, the leader’s output could be significantly reduced after deregulation. By using the unique data of the insuranc...

  13. Complement System Part II: Role in Immunity

    Science.gov (United States)

    Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

    2015-01-01

    The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. PMID:26074922

  14. The Epidermal Growth Factor Receptor Is a Regulator of Epidermal Complement Component Expression and Complement Activation

    DEFF Research Database (Denmark)

    Abu-Humaidan, Anas H A; Ananthoju, Nageshwar; Mohanty, Tirthankar

    2014-01-01

    The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin...

  15. Complement modulation of T cell immune responses during homeostasis and disease.

    Science.gov (United States)

    Clarke, Elizabeth V; Tenner, Andrea J

    2014-11-01

    The complement system is an ancient and critical effector mechanism of the innate immune system as it senses, kills, and clears infectious and/or dangerous particles and alerts the immune system to the presence of the infection and/or danger. Interestingly, an increasing number of reports have demonstrated a clear role for complement in the adaptive immune system as well. Of note, a number of recent studies have identified previously unknown roles for complement proteins, receptors, and regulators in T cell function. Here, we will review recent data demonstrating the influence of complement proteins C1q, C3b/iC3b, C3a (and C3aR), and C5a (and C5aR) and complement regulators DAF (CD55) and CD46 (MCP) on T cell function during homeostasis and disease. Although new concepts are beginning to emerge in the field of complement regulation of T cell function, future experiments should focus on whether complement is interacting directly with the T cell or is having an indirect effect on T cell function via APCs, the cytokine milieu, or downstream complement activation products. Importantly, the identification of the pivotal molecular pathways in the human systems will be beneficial in the translation of concepts derived from model systems to therapeutic targeting for treatment of human disorders. © 2014 Society for Leukocyte Biology.

  16. The C-type lectin of the aggrecan G3 domain activates complement.

    Directory of Open Access Journals (Sweden)

    Camilla Melin Fürst

    Full Text Available Excessive complement activation contributes to joint diseases such as rheumatoid arthritis and osteoarthritis during which cartilage proteins are fragmented and released into the synovial fluid. Some of these proteins and fragments activate complement, which may sustain inflammation. The G3 domain of large cartilage proteoglycan aggrecan interacts with other extracellular matrix proteins, fibulins and tenascins, via its C-type lectin domain (CLD and has important functions in matrix organization. Fragments containing G3 domain are released during normal aggrecan turnover, but increasingly so in disease. We now show that the aggrecan CLD part of the G3 domain activates the classical and to a lesser extent the alternative pathway of complement, via binding of C1q and C3, respectively. The complement control protein (CCP domain adjacent to the CLD showed no effect on complement initiation. The binding of C1q to G3 depended on ionic interactions and was decreased in D2267N mutant G3. However, the observed complement activation was attenuated due to binding of complement inhibitor factor H to CLD and CCP domains. This was most apparent at the level of deposition of terminal complement components. Taken together our observations indicate aggrecan CLD as one factor involved in the sustained inflammation of the joint.

  17. Structural and functional characterization of human complement factor P

    DEFF Research Database (Denmark)

    Pedersen, Dennis

    not yet been resolved. This PhD-thesis provide structural understanding of the FP mediated stabilization of the AP C3 convertase. Furthermore, functional studies involving oligomeric and monomeric FP variants have helped us to understand the importance of FP oligomerization for the primary functions of FP...... of complement by stabilizing the C3 convertase complex (C3bBb). FP has also been suggested to serve as a pattern recognition molecule for the initiation of the alternative pathway. However, the molecular mechanisms of FP remain unclear due to its oligomeric nature and hence the atomic structure of FP has...

  18. Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs.

    Science.gov (United States)

    Mentzel, Caroline M Junker; Cardoso, Tainã Figueiredo; Pipper, Christian Bressen; Jacobsen, Mette Juul; Jørgensen, Claus Bøttcher; Cirera, Susanna; Fredholm, Merete

    2018-02-01

    The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3) amount of retroperitoneal adipose tissue (RPATa). Although it is generally accepted that increasing amount of RPATa is 'unhealthy', a direct comparison of the relative impact of the three obesity-related phenotypes on gene expression has, to our knowledge, not been performed previously. We have used multiple linear models to analyze altered gene expression of selected obesity-related genes in tissues collected from 19 female pigs phenotypically characterized with respect to the obesity-related phenotypes. Gene expression was assessed by high-throughput qPCR in RNA from liver, skeletal muscle and abdominal adipose tissue. The stringent statistical approach used in the study has increased the power of the analysis compared to the classical approach of analysis in divergent groups of individuals. Our approach led to the identification of key components of cellular pathways that are modulated in the three tissues in association with changes in the three obesity-relevant phenotypes (BMI, SATa and RPATa). The deregulated pathways are involved in biosynthesis and transcript regulation in adipocytes, in lipid transport, lipolysis and metabolism, and in inflammatory responses. Deregulation seemed more comprehensive in liver (23 genes) compared to abdominal adipose tissue (10 genes) and muscle (3 genes). Notably, the study supports the notion that excess amount of intra-abdominal adipose tissue is associated with a greater metabolic disease risk. Our results provide molecular support for this notion by demonstrating that increasing amount of RPATa has a higher impact on perturbation of cellular pathways influencing obesity and obesity-related metabolic traits compared to increase

  19. Intracellular Complement Activation Sustains T Cell Homeostasis and Mediates Effector Differentiation

    Science.gov (United States)

    Liszewski, M. Kathryn; Kolev, Martin; Le Friec, Gaelle; Leung, Marilyn; Bertram, Paula G.; Fara, Antonella F.; Subias, Marta; Pickering, Matthew C.; Drouet, Christian; Meri, Seppo; Arstila, T. Petteri; Pekkarinen, Pirkka T.; Ma, Margaret; Cope, Andrew; Reinheckel, Thomas; Rodriguez de Cordoba, Santiago; Afzali, Behdad; Atkinson, John P.; Kemper, Claudia

    2013-01-01

    Summary Complement is viewed as a critical serum-operative component of innate immunity, with processing of its key component, C3, into activation fragments C3a and C3b confined to the extracellular space. We report here that C3 activation also occurred intracellularly. We found that the T cell-expressed protease cathepsin L (CTSL) processed C3 into biologically active C3a and C3b. Resting T cells contained stores of endosomal and lysosomal C3 and CTSL and substantial amounts of CTSL-generated C3a. While “tonic” intracellular C3a generation was required for homeostatic T cell survival, shuttling of this intracellular C3-activation-system to the cell surface upon T cell stimulation induced autocrine proinflammatory cytokine production. Furthermore, T cells from patients with autoimmune arthritis demonstrated hyperactive intracellular complement activation and interferon-γ production and CTSL inhibition corrected this deregulated phenotype. Importantly, intracellular C3a was observed in all examined cell populations, suggesting that intracellular complement activation might be of broad physiological significance. PMID:24315997

  20. Today or not today: Deregulating the Russian gas sector

    International Nuclear Information System (INIS)

    Grigoryev, Yuli

    2007-01-01

    Although Russia is the world's biggest producer of natural gas, its ability to maintain timely and reliable supply to meet the growing global demand has come under question in recent months. The gas war with Ukraine notwithstanding, concern has been raised by a number of observers that underinvestment in the gas sector will lead to a systemic failure of the state monopolist OAO Gazprom to increase or even maintain current levels of production. Yet with a quarter of European gas coming from Russia, and with increasing presence of Gazprom in European downstream operations (such as Germany, Hungary, and other CIS states) as well as seemingly closer ties with Algeria, another major supplier of gas to Europe, there has been a strong reaction from Europe's policy-makers to decrease dependence on Russian gas. Deregulating and liberalising the gas sector would see the lifting of restrictions to foreign or independent investors wishing to gain access to Russian reserves, as well as the unhindered access to the pipeline infrastructure and export markets. It would also signal the unbundling of Gazprom and an end to the artificially low price of gas to the domestic consumer. This paper discusses whether deregulation is the optimal way to raise capital, attract investment and increase supply security for Russia's Western neighbours. In doing so, the paper identifies the objectives of the EU as the importer whilst trying to align them with the objectives of the Russian Federation as the exporter, in the current political context

  1. A novel approach for modeling deregulated electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Ofir D., E-mail: rubino@agri.huji.ac.i [Department of Agricultural Economics and Management, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel); Babcock, Bruce A., E-mail: babcock@iastate.ed [Department of Economics, Iowa State University, 578F Heady Hall, Ames, IA 50011-1070 (United States); Center for Agricultural and Rural Development (CARD), Iowa State University, Ames, IA 50011-1070 (United States)

    2011-05-15

    The theoretical framework developed in this study allows development of a model of deregulated electricity markets that explains two familiar empirical findings; the existence of forward premiums and price-cost markups in the spot market. This is a significant contribution because electricity forward premiums have been previously explained exclusively by the assumptions of perfect competition and risk-averse behavior while spot markups are generally the outcome of a body of literature assuming oligopolistic competition. Our theoretical framework indicates that a certain premium for forward contracting is required for efficient allocation of generation capacity. However, due to the uniqueness of electricity and the design of deregulated electricity markets this premium might be substantially higher than its optimal level. - Research highlights: {yields} The state of knowledge regarding modeling electricity markets is incomplete. {yields} Electricity forward premiums are not necessarily driven by risk aversion. {yields} Efficiency in production requires a certain premium for forward contracting. {yields} It is likely that market premiums are substantially higher than their optimal level. {yields} Policy regulation should not seek to eliminate forward premium entirely.

  2. A novel approach for modeling deregulated electricity markets

    International Nuclear Information System (INIS)

    Rubin, Ofir D.; Babcock, Bruce A.

    2011-01-01

    The theoretical framework developed in this study allows development of a model of deregulated electricity markets that explains two familiar empirical findings; the existence of forward premiums and price-cost markups in the spot market. This is a significant contribution because electricity forward premiums have been previously explained exclusively by the assumptions of perfect competition and risk-averse behavior while spot markups are generally the outcome of a body of literature assuming oligopolistic competition. Our theoretical framework indicates that a certain premium for forward contracting is required for efficient allocation of generation capacity. However, due to the uniqueness of electricity and the design of deregulated electricity markets this premium might be substantially higher than its optimal level. - Research highlights: → The state of knowledge regarding modeling electricity markets is incomplete. → Electricity forward premiums are not necessarily driven by risk aversion. → Efficiency in production requires a certain premium for forward contracting. → It is likely that market premiums are substantially higher than their optimal level. → Policy regulation should not seek to eliminate forward premium entirely.

  3. Bluewater Power goes ERP route to address deregulation : case study

    Energy Technology Data Exchange (ETDEWEB)

    Broad, K. [Bluewater Power Distribution Corp., Sarnia, ON (Canada)

    2009-05-15

    Bluewater Power Distribution Corporation distributes electricity to 35,000 customers in southwestern Ontario, including residential customers, large industries and commercial establishments. Their distribution system network consists of more than 344 miles of overhead wires and 125 miles of underground wires. The company employs more than 90 full-time people and is the result of a merger of six local utilities in year 2000. Ontario's energy market was preparing to deregulate at the time of the merger. Under the deregulation rules, utilities in the province were required to provide unbundled bills and exchange customer electronic business transactions with energy retailers. New rules opened up the cost of power on the wholesale side, requiring utilities to conduct wholesale settlements with the Independent Electricity System Operator (IESO). The IESO manages Ontario's bulk electricity power system and operates the wholesale market. This article described the solution that Bluewater Power's information technology (IT) team found to support Ontario's local market, meet regulatory demands and adapt to future regulatory changes.

  4. Productivity growth and deregulation of Japanese electricity distribution

    International Nuclear Information System (INIS)

    Goto, Mika; Sueyoshi, Toshiyuki

    2009-01-01

    Deregulation of Japanese electric power industry began in 1995. After the amendment of Electricity Utility Industry Law in 1995, competition was partially introduced in a generation sector and retail competition started from 2000. Eligibility to choose suppliers was gradually extended from larger to smaller customers. As of 2008, almost all customers except households can choose their electricity suppliers. Based upon both previous implementation result of competition policy and review on their achievement, Japanese government will begin new policy debate in 2013 to assess further retail competition which includes household customers. To prepare for policy suggestion on the future electric power industry, this study examines the cost structure of Japanese electricity distribution. For the purpose, we estimate a multi-product translog cost function of Japanese electricity distribution from 1983 to 2003. Using the estimated cost function, we calculate several economic measures such as productivity growth, technical change and economies of scale and scope. The empirical results of this study indicate the improvement in productivity growth after deregulation.

  5. Effect of demand management on regulated and deregulated electricity sectors

    International Nuclear Information System (INIS)

    Fahrioglu, Murat

    2016-01-01

    Our society derives a quantifiable benefit from electric power. In particular, forced outages or blackouts have enormous consequences on society, one of which is loss of economic surplus. The society relies on having a continuous supply of electrical energy. Some customers may willingly risk this continuous supply and participate in demand management programs for electrical power. If the power system grid is in trouble, electric utilities need to have demand relief. Customers willing to reduce their demand to help the system can receive an incentive fee for helping the utilities. Demand relief can be system wide or location specific. Sometimes it can be more effective to fix the electrical demand vs. supply imbalance from the demand side. The value of demand management contracts is greatly affected by customer location. Inclusion of locational attributes into the contract design procedure increases the effectiveness of the contracts by helping a utility get more value from its demand management programs. Independent System Operators and regulators, among others, can also benefit from effective demand management. This paper will investigate how this type of demand management contracts can help the electricity sector both in regulated and deregulated environments. - Highlights: • Demand management can help prevent forced electricity outages. • Both electric utilities and ISOs can use demand management. • Regulated and deregulated electricity sectors can benefit from demand management. • Demand management contracts can be effectively used in power system grids.

  6. Competition and deregulation in electricity : the national and continental dimension

    International Nuclear Information System (INIS)

    Garant, D.

    2000-01-01

    Some of the recent developments with Hydro-Quebec in terms of moving towards a deregulated competitive market were presented. In June 2000, the Quebec National Assembly passed legislation allowing for power generation and wholesale supply of electricity within Quebec will to be a deregulated business based on the gradual introduction of a competitive, contested market at the wholesale level. This legislation mitigates Hydro-Quebec's market power by legislating a long term fixed price supply contract between Hydro-Quebec's generation and distribution groups, operating as a functionally separate division within corporate Hydro-Quebec. Hydro-Quebec's market power in generation is 36,000 MW, the bulk of which will be committed to the Quebec distribution market at a fixed price of about 2.8 cents per kWh. Hydro-Quebec will maintain the rights to develop large scale hydro in Quebec if the development meets conditions of economic viability, environmental soundness and is locally acceptable. Hydro-Quebec is also expanding into new areas of generation such as wind power. The electric utility also believes it can play a role in Atlantic Canada by trading and moving off-peak and on-peak energy by using the storage capacity of their large hydro reservoirs

  7. The impact of deregulation on the US nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Baratta, A.J. [Pennsylvania State Univ., Nuclear Safety Center, University Park, PA (United States)

    2001-07-01

    In the United States, the electric utility industry is undergoing a dramatic shift away from a tightly regulated monopoly to a free market system. The impact on the nuclear utility industry of deregulation coupled with recent changes in the nuclear regulatory environment has had a dramatic impact on the future of nuclear power in the United States. Utilities have been broken up into separate generation, transmission, and distribution companies and are now allowed to sell electricity outside of their former service areas. As economic deregulation has occurred, the U.S. Nuclear Regulatory Commission has also adopted a new approach to regulation -- risk informed regulation. The implementation of risk-informed regulation has resulted in the adoption of a new regulatory format that attempts to highlight those areas having greatest risk significance. This paper explores these and other changes that have resulted because of the changing economic and regulatory environment for nuclear energy and examines their impact on the future of nuclear energy in the United States. (author)

  8. Generation capacity adequacy in deregulated markets : options for Alberta

    International Nuclear Information System (INIS)

    Ayres, M.

    2004-01-01

    The Canadian Energy Research Institute (CERI) is a Calgary-based non-profit organization that conducts studies on energy and related environmental issues to help Canadian business and government organizations. This paper summarized the information in a two volume CERI study report which assessed generation capacity issues in deregulated electricity markets in Canada. The study observed the restructuring experience in several jurisdictions and described how, or if, energy-only markets are succeeding in ensuring capacity additions. Supply-side and demand-side mechanisms have been proposed as solutions to address these problems. Theoretical and practical issues of adequacy that are most relevant from a Canadian perspective were presented. In fully developed energy markets, the price of energy reflects scarcity. When generating resources are abundant prices are low. Since investment decisions are based on price expectations, it is unlikely that deregulated markets in their current state can offer adequate generation for the long term. It was concluded that long-term investment will occur with competitive markets and by adding a capacity mechanism to the market design. tabs., figs

  9. Deregulation and internationalisation - impact on the Swedish nuclear industry

    International Nuclear Information System (INIS)

    Haukeland, Sverre R.

    2010-01-01

    The deregulation of the Swedish electricity market in 1996 was well known in advance, and the nuclear power plants in Sweden, as well as their main suppliers, made early preparations for a this new situation. In a study - performed by the author at Malardalen University in Sweden - it is concluded that the electricity industry, including the nuclear power plants, was fundamentally transformed in conjunction with market liberalisation. Two large foreign companies, E-on and Fortum, entered the Swedish market and became part-owners of the nuclear plants. After deregulation, the electricity market in Sweden is dominated by these two companies and the large national company Vattenfall. Similarly, Vattenfall has recently grown into an international energy company, acquiring generation capacity in Northern Europe outside of Sweden, including nuclear power plants in Germany. Restructuring of the nuclear industry on the supplier side started in the 1980's, when the Swedish company ASEA and BBC of Switzerland merged to become ABB. Several years later the Swedish nuclear plant supplier ABB-Atom became part of Westinghouse Electric Company, today owned by Toshiba. The Swedish experience thus confirms an international trend of mergers and consolidation in the nuclear industry. (authors)

  10. Electricity deregulation, spot price patterns and demand-side management

    International Nuclear Information System (INIS)

    Li, Y.; Flynn, P.C.

    2006-01-01

    This paper examines extensive hourly or half-hourly power price data from 14 deregulated power markets. It analyzes average diurnal patterns, relationship to system load, volatility, and consistency over time. Diurnal patterns indicate the average price spread between off-peak and on-peak and weekend vs. weekday power consumption. Volatility is measured by price velocity: the average normalized hourly change in power price, calculated daily. The calculated price velocity is broken down into an expected component that arises from the diurnal pattern and an unexpected component that arises from unknown factors. The analysis reveals significant differences among markets, suggesting that demand-side management (DSM) of power consumption is far more difficult in some markets than in others. At one extreme, Spain, Britain and Scandinavia show consistent diurnal price patterns, a stable relationship between price and system load, and a low unexplained component of price volatility. A power consumer in these markets could form a reasonable expectation of a reward for DSM of elective power consumption. At the other extreme, two markets in Australia show erratic diurnal price patterns from year to year, low correlation between price and system load, and a high amount of unexpected price velocity. A power consumer in these markets would have far greater difficulty in realizing a benefit from DSM. Markets that experienced one period of very high prices without a clear external cause, such as California and Alberta, appear to have a significant longer-term erosion of public support for deregulation. (author)

  11. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Desrochers, J.P.

    2002-01-01

    An overview of the first year of electric power industry deregulation in Alberta was presented. The way in which electricity is bought and sold in Ontario and throughout North America is changing. Costs are no longer fixed and regulated. Electricity is becoming a commodity with high levels of price volatility. The paper presented hedging options for Alberta consumers, contracting lessons, market issues and lessons for Ontario. A comparison of Alberta's deregulation schedule with that of Ontario's was included. One year after market opening in Alberta, power prices have dropped significantly. There is a greater than expected demand side response, increased development in power generation, and a decrease in natural gas prices. Issues that still need to be addressed in Alberta include billing and load settlement issues, invoicing/billing standards, the lack of competition at the retail level, and future balancing of pool charges. Energy Advantage Inc. (EA) does not foresee the same drastic increase in price as seen in Alberta market opening, but suggests that uncertainty and volatility will exist in Ontario. In Alberta, customers who did nothing and stayed on default were the ones who benefited, but took a great risk. EA suggests that customers must understand how and when they use electricity, how much is used during on- and off-peak hours, and in the summer versus the winter. When electricity is priced hourly, it is important to know consumption patterns. 7 figs

  12. The impact of deregulation on the US nuclear industry

    International Nuclear Information System (INIS)

    Baratta, A.J.

    2001-01-01

    In the United States, the electric utility industry is undergoing a dramatic shift away from a tightly regulated monopoly to a free market system. The impact on the nuclear utility industry of deregulation coupled with recent changes in the nuclear regulatory environment has had a dramatic impact on the future of nuclear power in the United States. Utilities have been broken up into separate generation, transmission, and distribution companies and are now allowed to sell electricity outside of their former service areas. As economic deregulation has occurred, the U.S. Nuclear Regulatory Commission has also adopted a new approach to regulation -- risk informed regulation. The implementation of risk-informed regulation has resulted in the adoption of a new regulatory format that attempts to highlight those areas having greatest risk significance. This paper explores these and other changes that have resulted because of the changing economic and regulatory environment for nuclear energy and examines their impact on the future of nuclear energy in the United States. (author)

  13. Maintenance cost models in deregulated power systems under opportunity costs

    International Nuclear Information System (INIS)

    Al-Arfaj, K.; Dahal, K.; Azaiez, M.N.

    2007-01-01

    In a centralized power system, the operator is responsible for scheduling maintenance. There are different types of maintenance, including corrective maintenance; predictive maintenance; preventive maintenance; and reliability-centred maintenance. The main cause of power failures is poor maintenance. As such, maintenance costs play a significant role in deregulated power systems. They include direct costs associated with material and labor costs as well as indirect costs associated with spare parts inventory, shipment, test equipment, indirect labor, opportunity costs and cost of failure. In maintenance scheduling and planning, the cost function is the only component of the objective function. This paper presented the results of a study in which different components of maintenance costs were modeled. The maintenance models were formulated as an optimization problem with single and multiple objectives and a set of constraints. The maintenance costs models could be used to schedule the maintenance activities of power generators more accurately and to identify the best maintenance strategies over a period of time as they consider failure and opportunity costs in a deregulated environment. 32 refs., 4 tabs., 4 figs

  14. GLUCOCORTICOSTEROIDS' EFFECT UPON THE COMPLEMENT LEVEL

    Directory of Open Access Journals (Sweden)

    Voja Pavlovic

    2001-03-01

    Full Text Available The effect of high doses of cortisol upon the level of the overall complements'hemolytic activity and particular complements' components is studies. The experimentsinvolved guinea pigs of male sex of the body mass from 300 to 400 g, namelythose that have not been treated by anything so far. The doses of hydrocortisone(Hemofarm DD were also used for the experiment. The overall complements'activity was determined by testing the capabilities of a series of various solutions ofthe guinea pigs' serum to separate sheep erythrocytes that were made sensitive byrabbit anti-erythrocyte antibodies. The determination of the C1, C2, C3 and C4complements' components was done by the method of the quantitative diffusion ofthe radial type by using the Partigen blocks Behringwerke AG. The series comprised25 guinea pigs of male sex. The low cortisol level rapidly increase the overallhemolytic activity of the complements of the C1 est erase concentration. Along withthe cortisol dose increase the overall hemolytic complements' activity is dropping aswell as that of the C1, C2, C3 and C4 complements' components.

  15. Pathogens' toolbox to manipulate human complement.

    Science.gov (United States)

    Fernández, Francisco J; Gómez, Sara; Vega, M Cristina

    2017-12-14

    The surveillance and pathogen fighting functions of the complement system have evolved to protect mammals from life-threatening infections. In turn, pathogens have developed complex molecular mechanisms to subvert, divert and evade the effector functions of the complement. The study of complement immunoevasion by pathogens sheds light on their infection drivers, knowledge that is essential to implement therapies. At the same time, complement evasion also acts as a discovery ground that reveals important aspects of how complement works under physiological conditions. In recent years, complex interrelationships between infection insults and the onset of autoimmune and complement dysregulation diseases have led to propose that encounters with pathogens can act as triggering factors for disease. The correct management of these diseases involves the recognition of their triggering factors and the development and administration of complement-associated molecular therapies. Even more recently, unsuspected proteins from pathogens have been shown to possess moonlighting functions as virulence factors, raising the possibility that behind the first line of virulence factors there be many more pathogen proteins playing secondary, helping and supporting roles for the pathogen to successfully establish infections. In an era where antibiotics have a progressively reduced effect on the management and control of infectious diseases worldwide, knowledge on the mechanisms of pathogenic invasion and evasion look more necessary and pressing than ever. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress

    DEFF Research Database (Denmark)

    Fanelli, Giorgia; Gonzalez-Cordero, Anai; Gardner, Peter J

    2017-01-01

    induced-pluripotent stem cell (iPSC)-derived RPE cells, particularly with regard to the complement pathway. We focused on collectin-11 (CL-11), a pattern recognition molecule that can trigger complement activation in renal epithelial tissue. We found evidence of constitutive and hypoxia-induced expression......, failed to activate complement. The presence of CL-11 in healthy murine and human retinal tissues confirmed the biological relevance of CL-11. Our data describe a new trigger mechanism of complement activation that could be important in disease pathogenesis and therapeutic interventions....

  17. Serum complement changes during double-blind food challenges in children with a history of food sensitivity.

    Science.gov (United States)

    Martin, M E; Guthrie, L A; Bock, S A

    1984-04-01

    Serum levels of C3, C4, factor B, properdin, total hemolytic complement and alternative-pathway hemolytic activity were measured before and after double-blind food challenge in 23 children with impressive histories of adverse reactions to foods. The 23 subjects had 11 positive food challenges and 12 negative food challenges. Nine patients with reagin-mediated positive food challenges showed increases in all six complement assays after double-blind food challenge, while the group with negative food challenges showed decreases in five of the six assays. The difference between the two groups for complement changes after double-blind food challenge was significant only for the alternative-pathway assay. Individual subject analysis revealed markedly heterogeneous changes in direction and magnitude within both groups for all complement assays. Therefore, it is concluded that measurement of serum complement levels is not a useful test for the clinical evaluation of a patient with suspected food sensitivity.

  18. Genetics Home Reference: complement component 2 deficiency

    Science.gov (United States)

    ... Topic: Immune System and Disorders Health Topic: Lupus Genetic and Rare Diseases Information Center (1 link) Complement component 2 deficiency Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (6 ...

  19. Air pollution effects due to deregulation of the electric industry

    Science.gov (United States)

    Davoodi, Khojasteh Riaz

    The Energy Policy Act of 1992 introduced the concept of open-access into the electric utility industry which allows privately-owned utilities to transmit power produced by non-utility generators and independent power producers (IPPs). In April 1996, the Federal Energy Regulatory Commission (FERC) laid down the final rules (Orders No. 888 & No. 889), which required utilities to open their transmission lines to any power producer and charge them no more than what they pay for the use of their own lines. These rules set the stage for the retail sale of electricity to industrial, commercial and residential utility customers; non-utility generators (Nugs); and power marketers. These statutory, regulatory and administrative changes create for the electric utility industry two different forces that contradict each other. The first is the concept of competition among utility companies; this places a greater emphasis on electric power generation cost control and affects generation/fuel mix selection and demand side management (DSM) activities. The second force, which is converse to the first, is that utilities are major contributors to the air pollution burden in the United States and environmental concerns are forcing them to reduce emissions of air pollutants by using more environmentally friendly fuels and implementing energy saving programs. This study evaluates the impact of deregulation within the investor owned electric utilities and how this deregulation effects air quality by investigating the trend in demand side management programs and generation/fuel mix. A survey was conducted of investor owned utilities and independent power producers. The results of the survey were analyzed by analysis of variance and regression analysis to determine the impact to Air Pollution. An air Quality Impact model was also developed in this study. This model consists of six modules: (1) demand side management and (2) consumption of coal, (3) gas, (4) renewable, (5) oil and (6

  20. Core designs for the de-regulated market

    International Nuclear Information System (INIS)

    Almberger, J.; Bernro, R.; Pettersson, H.

    1999-01-01

    Complete text of publication follows: The electricity market deregulation in the Nordic countries encourages innovations and cost reductions for power production in the Vattenfall reactors. The competition on the electricity market is strong, electricity price reductions dramatic and uncertainties about the future power demand is large. In the fuel area this situation has given increased attention to traditional areas like flexibility in power production, improved core designs, need for margins (improved fuel designs), improved surveillance, decreased lead times. At Vattenfall new fuel designs are already being implemented following the last fuel purchase, for which flexibility and margins, were given high values in the evaluations with the multipurpose task of eliminating fuel related problems and meeting the future market situation. This strategy has given Vattenfall a flying start to meeting the demands of the de-regulated market. What has been added are broad studies undertaken to investigate the various route into the future with respect to finding the most effective strategies for fuel and core design and optimization. In the present paper the Vattenfall priorities for fuel designs and margins are presented in a schematic manner summarizing the results of the last fuel purchase and also presenting the current program for LFAs. Technical limitations, licensing and R and D aspects, with respect to improving the fuel utilization will be mentioned. The main focus in the paper is on the broad study carried out in the PWR core design area. Driven by the relatively low power demand various possibilities for higher production flexibility have been investigated specifically extended coast-down, coast-up and yearly load follow. Further to reduce the costs for fuel consumption improvements in core designs have been studied: improved low leakage loading patterns, low enriched end zones, improved Gd designs etc. Main results and conclusions of the core design studies will

  1. Complement and thrombosis in the antiphospholipid syndrome.

    Science.gov (United States)

    Oku, Kenji; Nakamura, Hiroyuki; Kono, Michihiro; Ohmura, Kazumasa; Kato, Masaru; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Amengual, Olga; Atsumi, Tatsuya

    2016-10-01

    The involvement of complement activation in the pathophysiology of antiphospholipid syndrome (APS) was first reported in murine models of antiphospholipid antibody (aPL)-related pregnancy morbidities. We previously reported that complement activation is prevalent and may function as a source of procoagulant cell activation in the sera of APS patients. Recently, autoantibodies against C1q, a component of complement 1, were reported to be correlated with complement activation in systemic lupus erythematosus. These antibodies target neoepitopes of deformed C1q bound to various molecules (i.e., anionic phospholipids) and induce accelerated complement activation. We found that anti-C1q antibodies are more frequently detected in primary APS patients than in control patients and in refractory APS patients with repeated thrombotic events. The titer of anti-C1q antibodies was significantly higher in refractory APS patients than in APS patients without flare. The binding of C1q to anionic phospholipids may be associated with the surge in complement activation in patients with anti-C1q antibodies when triggered by 'second-hit' biological stressors such as infection. Such stressors will induce overexpression of anionic phospholipids, with subsequent increases in deformed C1q that is targeted by anti-C1q antibodies. Copyright © 2016. Published by Elsevier B.V.

  2. Power plant operation and management in a deregulated market

    Energy Technology Data Exchange (ETDEWEB)

    Carraretto, Cristian [Department of Mechanical Engineering, University of Padova, Via Venezia, 1-35131 Padova (Italy)

    2006-05-15

    This paper analyzes the influence of electricity deregulation on the design, operation and management of the power plants owned by strategic and non-strategic producers. After a sensitivity analysis aimed at finding market conditions of profitable operation for thermal and hydroelectric power plants, a Nash-equilibrium market model is used to determine producers' optimum strategies, depending on their relative market power and overall production characteristics. Attention is then focused on the operation of single thermal power plants. Their short-term management plans and consequent effects on emission levels and residual life are described. The available reserve for primary and secondary control deriving from producers' market strategies is discussed. Some design options to improve combined cycles contribution to reserve service are finally described. The paper discusses these problems with a general approach, and uses many cases and examples derived from the current Italian scenario. (author)

  3. Power plant operation and management in a deregulated market

    International Nuclear Information System (INIS)

    Carraretto, Cristian

    2006-01-01

    This paper analyzes the influence of electricity deregulation on the design, operation and management of the power plants owned by strategic and non-strategic producers. After a sensitivity analysis aimed at finding market conditions of profitable operation for thermal and hydroelectric power plants, a Nash-equilibrium market model is used to determine producers' optimum strategies, depending on their relative market power and overall production characteristics. Attention is then focused on the operation of single thermal power plants. Their short-term management plans and consequent effects on emission levels and residual life are described. The available reserve for primary and secondary control deriving from producers' market strategies is discussed. Some design options to improve combined cycles contribution to reserve service are finally described. The paper discusses these problems with a general approach, and uses many cases and examples derived from the current Italian scenario. (author)

  4. Pricing and University Autonomy: Tuition Deregulation in Texas

    Directory of Open Access Journals (Sweden)

    Jeongeun Kim

    2016-04-01

    Full Text Available This paper investigates changes in tuition policies in the wake of tuition deregulation in Texas, which in 2003 transferred tuition-setting authority from the state legislature to institutions. We find that price increases accelerated, particularly at the most selective institutions. Institutions also began differentiating price by undergraduate program, raising relative prices for the most costly and lucrative majors, including engineering, business, nursing, and architecture. Price increases were particularly large for institutions with the highest initial costs and for programs with a high earnings premium within institutions, though lower for institutions with more low-income students. These distinctions suggest that public postsecondary institutions respond to microeconomic incentives when given greater autonomy to set price, and take some measures to alleviate impacts on low-income students. The Texas experience suggests that decentralized price-setting generates greater price differentiation within the public higher education system, both across and within institutions.

  5. Power quality and reliability issues in a deregulated energy market

    International Nuclear Information System (INIS)

    Huggins, M.J.

    1999-01-01

    The challenge of maintaining power quality and reliability in Ontario's new competitive electricity market was the focus of this paper. The intention of Ontario's deregulation is to lower costs and give customers more power and choice. However, some fear that costs pressures may lead to poorer quality. This paper reviewed the causes, costs, and responsibilities, and made some suggestions concerning how customers can protect their interests as the market opens. It was suggested that in order to assure power quality, especially during the transition period, customers need to take care to design their systems and equipment to tolerate some quality variations. Conversely, utilities need to strive for at least minimum industry standards under most conditions. Contracts should be carefully crafted, with responsibilities for reliability and quality clearly stated. 2 refs

  6. Impact of electricity market deregulation on information systems

    International Nuclear Information System (INIS)

    Pharabod, E.; Berrier, M.

    2005-01-01

    Electricity market deregulation is based on un-bundling of activities between generation, transmission and distribution. In a very short time, mechanisms were put in place in order to allow the new market participants to buy and sell electricity. The market operation requires to exchange information at various time horizon, from yearly to real time exchanges, between various actors geographically distributed. The recent market opening to professional customers has also increased the amount of data involved. The information system developed by RTE to manage these data is organised around referential data base, internal and external exchange tools. It must be operated respecting confidentiality of commercial data and being non discriminatory with actors. The security of this information system is now a key issue for the electricity market operation. (authors)

  7. Do cost-sharing and entry deregulation curb pharmaceutical innovation?

    Science.gov (United States)

    Grossmann, Volker

    2013-09-01

    This paper examines the role of both cost-sharing schemes in health insurance systems and the regulation of entry into the pharmaceutical sector for pharmaceutical R&D expenditure and drug prices. The analysis suggests that both an increase in the coinsurance rate and stricter price regulations adversely affect R&D spending in the pharmaceutical sector. In contrast, entry deregulation may lead to higher R&D spending of pharmaceutical companies. The relationship between R&D spending per firm and the number of firms may be hump-shaped. In this case, the number of rivals which maximizes R&D expenditure per firm is decreasing in the coinsurance rate and increasing in labor productivity. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Natural gas deregulation: have the handcuffs really been removed?

    International Nuclear Information System (INIS)

    Kelley, T.D.

    1995-01-01

    The natural gas market in New York State was reviewed and characterized as being very competitive. A brief description of the New York State Electric and Gas Corp. (NYSEG) was given. As regards recent developments, in October 1993, the New York Public Service Commission (NYPSC) instituted a proceeding (93-G-0932) on the restructuring of the gas market. Several guidelines for market restructuring were established as a result. The guidelines were in respect to service to consumers, safety of distribution, environmental implications, consumer concerns, gas rates, regulation, and access for core customers. The speaker noted that these guidelines did not promote deregulation. Competitive issues faced by local gas distributors were enumerated. Among these were (1)service to core and non-core customers (2)transition costs, (3)streaming, (4)unbundling and repackaged services, (5)price differentiation, and (6)small customer aggregation. It was expected that marketers would oppose the Public Service Commission giving local gas distributors additional pricing flexibility

  9. Electricity pricing and load dispatching in deregulated electricity market

    International Nuclear Information System (INIS)

    Geerli; Niioka, S.; Yokoyama, R.

    2003-01-01

    A rapid move to a market-based electric power industry will significantly alter the structure of electricity pricing and system operation. In this paper, we consider a game of negotiation in the electricity market, involving electric utilities, independent power producers (IPPs) and large-scale customers. We analyze the two-level game strategies for the negotiation process between utilities, IPPs and customers. These have been previously recognized as a way to come up with a rational decision for competitive markets, in which players intend to maximize their own profits. The derived operation rules based on competition can be viewed as an extension of the conventional equal incremental cost method for the deregulated power system. The proposed approach was applied to several systems to verify its effectiveness. (Author)

  10. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Charach, L.

    2002-01-01

    This paper provides a 15 month assessment of Alberta's new competitive electricity market. It also presents lessons that Ontario customers could learn from Alberta's experience. The goal for restructuring is to achieve lower electricity prices, competitive retail markets, increased flexibility of contracts, and to remove investment risks from consumers. Alberta's restructured market includes power generation, high voltage transmission, low voltage transmission and retail sales. Economists agree that deregulation has brought lower prices and other consumer benefits despite some imperfections. After one year, prices in Alberta have gone down from $130/MWh to $30/MWh. Power supply has increased along with demand response, market competitiveness, liquidity, and thermal and economic efficiency. In 2001, Alberta was a net exporter of electricity. In 2001, it was ranked by the Center for Advancement of Energy Markets (CAEM) which ranks states and provinces by 22 attributes for how they are restructuring their power markets. Alberta ranked first overall in North America. Ontario ranked sixteenth. 4 tabs., 5 figs

  11. Steady state security assessment in deregulated power systems

    Science.gov (United States)

    Manjure, Durgesh Padmakar

    Power system operations are undergoing changes, brought about primarily due to deregulation and subsequent restructuring of the power industry. The primary intention of the introduction of deregulation in power systems was to bring about competition and improved customer focus. The underlying motive was increased economic benefit. Present day power system analysis is much different than what it was earlier, essentially due to the transformation of the power industry from being cost-based to one that is price-based and due to open access of transmission networks to the various market participants. Power is now treated as a commodity and is traded in an open market. The resultant interdependence of the technical criteria and the economic considerations has only accentuated the need for accurate analysis in power systems. The main impetus in security analysis studies is on efficient assessment of the post-contingency status of the system, accuracy being of secondary consideration. In most cases, given the time frame involved, it is not feasible to run a complete AC load flow for determining the post-contingency state of the system. Quite often, it is not warranted as well, as an indication of the state of the system is desired rather than the exact quantification of the various state variables. With the inception of deregulation, transmission networks are subjected to a host of multilateral transactions, which would influence physical system quantities like real power flows, security margins and voltage levels. For efficient asset utilization and maximization of the revenue, more often than not, transmission networks are operated under stressed conditions, close to security limits. Therefore, a quantitative assessment of the extent to which each transaction adversely affects the transmission network is required. This needs to be done accurately as the feasibility of the power transactions and subsequent decisions (execution, curtailment, pricing) would depend upon the

  12. Game-theoretic equilibrium analysis applications to deregulated electricity markets

    Science.gov (United States)

    Joung, Manho

    This dissertation examines game-theoretic equilibrium analysis applications to deregulated electricity markets. In particular, three specific applications are discussed: analyzing the competitive effects of ownership of financial transmission rights, developing a dynamic game model considering the ramp rate constraints of generators, and analyzing strategic behavior in electricity capacity markets. In the financial transmission right application, an investigation is made of how generators' ownership of financial transmission rights may influence the effects of the transmission lines on competition. In the second application, the ramp rate constraints of generators are explicitly modeled using a dynamic game framework, and the equilibrium is characterized as the Markov perfect equilibrium. Finally, the strategic behavior of market participants in electricity capacity markets is analyzed and it is shown that the market participants may exaggerate their available capacity in a Nash equilibrium. It is also shown that the more conservative the independent system operator's capacity procurement, the higher the risk of exaggerated capacity offers.

  13. BDI position on energy policy and energy market deregulation

    International Nuclear Information System (INIS)

    Kreklau, C.

    2003-01-01

    Secure energy supplies are indispensable for our modern way of life and our economy. Energy policy is a part of economic policy and must be shaped within the magic triangle of objectives, i.e. security, competitiveness, environmental compatibility. As a result of their outstanding role, electricity and natural gas, with respective shares of 70% in industrial energy use and 85% in energy costs, are in the focus of energy policy interest of the Federation of German Industries (BDI). One important development over the past few years has been the deregulation of the markets for electricity and gas. However, the markedly lower electricity rates to be paid by industry, commercial tariff consumers, and private customers are being offset by new burdens arising from government intervention and taxes. Other dirigistic interventions into the energy market by the red-green federal government since 1998, referred to as 'turning point of energy policy', are invalidating what market opening had been achieved. With a view to a sustainable energy policy for the future, BDI pleads in favor of a broad energy mix. In a mix neutral with respect to competition, this includes the classical energy sources, the renewables, and low-cost, environmentally friendly nuclear power. In principle, it is the forces of the market, coupled with responsible action, which are to steer further developments. On a European level, speedy implementation of the opening of the electricity and gas markets, as decided, should be urged. It is important that the leeway won as a result of deregulation not be constrained again by new regulations. More market, less regulation, and more direct responsibility must provide room for a powerful energy supply system under the premises of the triangle of objectives referred to above. (orig.) [de

  14. Public understanding of environmental impacts of electricity deregulation

    International Nuclear Information System (INIS)

    Johnson, Branden B.; Frank, Pamela G.

    2006-01-01

    Electricity deregulation has aroused concern that environmental quality might be harmed by consumer preferences for cheap, 'dirty' (e.g., coal) electricity products, despite the perhaps stronger influence of supply side policy on environmental impacts. This outcome depends on public understanding of the environmental impacts of their decisions, which this study explored with interviews, focus groups, and surveys in New Jersey. People had thought little about the topic, were unable to articulate how electricity production might affect the environment except in very general terms, and were mostly unwilling to guess whether deregulation's impacts would be negative, neutral or positive. Those who did guess expected negative impacts less than any other kind. Reactions to specific 'reasons' for expecting no, positive or negative impacts suggested that consumers had little structure to their mental models in this area; for example, people who thought positive-impact reasons were probably true were not necessarily likely to see negative-impact reasons as probably false. However, in the aggregate, people seemed to have a fairly consistent ranking of energy sources by expected negative environmental impacts. Earlier research found that consumers comparing two electricity products on environmental impacts reached different decisions if they had energy-source-only or energy-source-plus-emissions information. Although regulator-required 'environmental labels' for electricity products provide both source and emissions data, it is not clear that they do an adequate job of both alerting consumers to the possibility of negative environmental impacts and identifying the relative life-cycle impacts of different products so as to produce informed consumer decisions

  15. The economics of energy storage in 14 deregulated power markets

    International Nuclear Information System (INIS)

    Figueiredo, F.C.; Flynn, P.C.; Cabral, E.A.

    2006-01-01

    In regulated power markets, electricity is stored to better utilize existing generation and to defer costly investment in generation. The justification is a reduction in the overall regulated price of power compared to the alternative investment in new primary generation. However, any storage of electrical power also involves a capital investment and incurs the cost of inefficiency. In deregulated energy markets, the sale of electricity or ancillary services from pumped storage can be evaluated based on each individual project. The economic basis for power storage is that power is purchased during periods of low price and resold during periods of high price. This study used historical power price data from 14 deregulated markets around the world to evaluate the economic incentive to use pumped storage for electrical energy. Each market was shown to have a unique average diurnal power price profile that results in a unique price spread for pumped storage. The diurnal price pattern and efficiency of storage was used to assess the net income potential from energy sales from pumped storage for each market. The markets were ranked in terms of the incentive to invest in pumped energy storage as well as on available revenue, and on potential return on investment. An optimal operating profile was illustrated in detail based on historical price patterns for one of the markets. The net income potential was then combined with the capital and operating cost of pumped storage. The adequacy of return on investment for pumped storage was analyzed by two different methods. The differences between markets stem from different diurnal power price patterns that reflect the generation mix, market design and participant behaviours. 17 refs., 7 tabs., 7 figs., 1 appendix

  16. Investments into plant replacements in a deregulated electricity market

    International Nuclear Information System (INIS)

    Elsaesser, R.F.

    2004-01-01

    The amendment to the Power Energy Act in April 1998 marked the complete deregulation of the electricity market in Germany. The debate is now beginning about ways and means to ensure new capital investments safeguarding the continuity of supply. The present power plant park has been characterized by a broad mix of primary energy sources and, admittedly, by some overcapacity as well. However, any further reduction of generating capacity will be at the expense of the continuity of supply. Although electricity prices in Germany are on the rise again after a clear drop, they have not yet reached a level sufficient for new investments. Only subsidized power plants are recovering their full costs. The question is for how long our economy is going to sustain this state of affairs. The balance among the energy policy goals of continuity of supply, environmental performance, and economic efficiency has been upset. In the period up until 2020, Germany alone will require approx. 37,000 MW of new generating capacity. Renewable and decentralized technologies alone do not constitute a sufficient and reliable alternative. However, there is the matter also of the practical feasibility of building the new power plants required. No experience is as yet available with re-investment cycles in the deregulated electricity market. Options are needed for a diversified structure of primary energy sources. There must be neither political definition of generating technologies nor exaggerated goals of environmental protection and climate protection. We advocate the free system of market prices and free access to the market. Major players able to guarantee sufficient security of investments are needed to cope with the challenges ahead. New investments with a life of thirty to forty years require a modicum of stability and realism in political framework conditions. (orig.)

  17. Economic use of a nuclear park in a deregulated market

    International Nuclear Information System (INIS)

    Eliasson, L.

    2000-01-01

    The deregulation of the electricity market has created a new situation for plant life management. In order to be competitive it is important to cut costs. All means to cut costs have to be used while still maintaining safety and production capacity. The possibilities to invest in modernization are limited to the absolute necessary modifications. All investments must be very thoroughly questioned and the money can only be spent where most benefit is gained. This means new prerequisites for the absolute necessary long strategic planning. New safety requirements from the regulatory body have to be discussed between the industry and the regulator. The cost of new requirements must be compared to the benefit for the safety. The regulator is today requested to carry out such analyses and do so in most cases. Still the electricity market is international and the requirements of the regulator must be harmonized on the whole market. The political threat against nuclear power is serious in many countries and it is important to continue working with public and political understanding and acceptance. Especially in Sweden a lot of effort is spent on trying to get harmonized taxes and environmental fees. Nuclear power is paying for all its costs and the external costs are already internalized. Still, at the deregulated market, nuclear power is competitive, creating positive cash flow, a good object for investments and environmentally favourable. Threats have to be removed to get prerequisites for long term strategic planning and investments. Steps in that direction will be increasing electricity demand, in the near future, which will make the prices to raise creating an improved economic situation. Also the very serious worries about climate change will strengthen the competitiveness of nuclear power. (author)

  18. Modulatory Role of Surface Coating of Superparamagnetic Iron Oxide Nanoworms in Complement Opsonization and Leukocyte Uptake

    DEFF Research Database (Denmark)

    Inturi, Swetha; Wang, Guankui; Chen, Fangfang

    2015-01-01

    demonstrated that neutrophils, monocytes, lymphocytes and eosinophils took up SPIO NWs, and the uptake was prevented by EDTA (a general complement inhibitor) and by antiproperdin antibody (an inhibitor of the alternative pathway of the complement system). Cross-linking and hydrogelation of SPIO NWs surface...... by epichlorohydrin decreased C3 opsonization in mouse serum, and consequently reduced the uptake by mouse leukocytes by more than 70% in vivo. Remarkably, the cross-linked particles did not show a decrease in C3 opsonization in human serum, but showed a significant decrease (over 60%) of the uptake by human...... leukocytes. The residual uptake of cross-linked nanoparticles was completely blocked by EDTA. These findings demonstrate species differences in complement-mediated nanoparticle recognition and uptake by leukocytes, and further show that human hemocompatibility could be improved by inhibitors of complement...

  19. Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

    Science.gov (United States)

    Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

    2018-01-04

    Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Francisella tularensis Confronts the Complement System

    Directory of Open Access Journals (Sweden)

    Susan R. Brock

    2017-12-01

    Full Text Available Francisella tularensis has developed a number of effective evasion strategies to counteract host immune defenses, not the least of which is its ability to interact with the complement system to its own advantage. Following exposure of the bacterium to fresh human serum, complement is activated and C3b and iC3b can be found covalently attached to the bacterial surface. However, the lipopolysaccharide and capsule of the F. tularensis cell wall prevent complement-mediated lysis and endow the bacterium with serum resistance. Opsonization of F. tularensis with C3 greatly increases its uptake by human neutrophils, dendritic cells and macrophages. Uptake occurs by an unusual looping morphology in human macrophages. Complement receptor 3 is thought to play an important role in opsonophagocytosis by human macrophages, and signaling through this receptor can antagonize Toll-like receptor 2-initiated macrophage activation. Complement C3 also determines the survival of infected human macrophages and perhaps other cell types. C3-opsonization of F. tularensis subsp. tularensis strain SCHU S4 results in greatly increased death of infected human macrophages, which requires more than complement receptor engagement and is independent of the intracellular replication by the pathogen. Given its entry into the cytosol of host cells, F. tularensis has the potential for a number of other complement-mediated interactions. Studies on the uptake C3-opsonized adenovirus have suggested the existence of a C3 sensing system that initiates cellular responses to cytosolic C3b present on invading microbes. Here we propose that C3 peptides enter the cytosol of human macrophages following phagosome escape of F. tularensis and are recognized as intruding molecular patterns that signal host cell death. With the discovery of new roles for intracellular C3, a better understanding of tularemia pathogenesis is likely to emerge.

  1. Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

    Science.gov (United States)

    Khattab, Ayman; Barroso, Marta; Miettinen, Tiera; Meri, Seppo

    2015-01-01

    Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood. PMID:25679788

  2. Anopheles midgut epithelium evades human complement activity by capturing factor H from the blood meal.

    Directory of Open Access Journals (Sweden)

    Ayman Khattab

    2015-02-01

    Full Text Available Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood.

  3. Deregulation of epidermal stem cell niche contributes to pathogenesis of non-healing venous ulcers

    Science.gov (United States)

    Nusbaum, Aron G.; Vukelic, Sasa; Krzyzanowska, Agata; Tomic-Canic, Marjana

    2014-01-01

    The epidermis is maintained by epidermal stem cells (ESC) that reside in distinct niches and contribute to homeostasis and wound closure. Keratinocytes at the non-healing edges of venous ulcers (VUs) are healing-incompetent, hyper-proliferative and non-migratory suggesting deregulation of ESCs. To date genes which regulate ESC niches have been studied in mice only. Utilizing microarray analysis of VU non-healing edges, we identified changes in expression of genes harboring regulation of ESCs and their fate. In a prospective clinical study of ten VUs, we confirmed suppression of the bone morphogenetic protein receptor and GATA binding protein3 as well as inhibitors of DNA-binding proteins 2 and 4. We also found decreased levels of phosphorylated glycogen synthase kinase 3, nuclear presence of ß-catenin and overexpression of its transcriptional target, c-myc indicating activation of the Wnt pathway. Additionally, we found down-regulation of leucine-rich repeats and immunoglobulin-like domains protein 1, a gene important for maintaining ESCs in a quiescent state, and absence of keratin 15, a marker of the basal stem cell compartment suggesting local depletion of ESCs. Our study shows that loss of genes important for regulation of ESCs and their fate along with activation of ß-catenin and c-myc in the VU may contribute to ESC deprivation and a hyper-proliferative, non-migratory, healing incapable wound edge. PMID:24635172

  4. Low level genome mistranslations deregulate the transcriptome and translatome and generate proteotoxic stress in yeast

    Directory of Open Access Journals (Sweden)

    Paredes João A

    2012-06-01

    Full Text Available Abstract Background Organisms use highly accurate molecular processes to transcribe their genes and a variety of mRNA quality control and ribosome proofreading mechanisms to maintain intact the fidelity of genetic information flow. Despite this, low level gene translational errors induced by mutations and environmental factors cause neurodegeneration and premature death in mice and mitochondrial disorders in humans. Paradoxically, such errors can generate advantageous phenotypic diversity in fungi and bacteria through poorly understood molecular processes. Results In order to clarify the biological relevance of gene translational errors we have engineered codon misreading in yeast and used profiling of total and polysome-associated mRNAs, molecular and biochemical tools to characterize the recombinant cells. We demonstrate here that gene translational errors, which have negligible impact on yeast growth rate down-regulate protein synthesis, activate the unfolded protein response and environmental stress response pathways, and down-regulate chaperones linked to ribosomes. Conclusions We provide the first global view of transcriptional and post-transcriptional responses to global gene translational errors and we postulate that they cause gradual cell degeneration through synergistic effects of overloading protein quality control systems and deregulation of protein synthesis, but generate adaptive phenotypes in unicellular organisms through activation of stress cross-protection. We conclude that these genome wide gene translational infidelities can be degenerative or adaptive depending on cellular context and physiological condition.

  5. The membrane attack complex of the complement system is essential for rapid wallerian degeneration

    NARCIS (Netherlands)

    Ramaglia, Valeria; King, Rosalind Helen Mary; Nourallah, Michelle; Wolterman, Ruud; de Jonge, Rosalein; Ramkema, Marja; Vigar, Miriam Ann; van der Wetering, Sandra; Morgan, Brian Paul; Troost, Dirk; Baas, Frank

    2007-01-01

    The complement (C) system plays an important role in myelin breakdown during Wallerian degeneration (WD). The pathway and mechanism involved are, however, not clear. In a crush injury model of the sciatic nerve, we show that C6, necessary for the assembly of the membrane attack complex (MAC), is

  6. X-ray repair cross complementing protein 1 in base excision repair

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour

    2012-01-01

    X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...

  7. Overview of the developments in the domestic airline industry in South Africa since market deregulation

    Directory of Open Access Journals (Sweden)

    Rose Luke

    2013-11-01

    Full Text Available Deregulation or liberalisation of air transport has had major global impacts on the domestic air transport markets, with effects ranging from stimulation to changes in the structure and functioning of these markets. In South Africa, deregulation has had wide-reaching effects on the domestic market. The purpose of this article was to investigate the current domestic air transport market. A literature review was performed to examine the effects of deregulation in other domestic air transport markets around the world. This was followed by a review of the South African domestic air transport market prior to deregulation in order to determine the changes that were made following deregulation. The ten-year period immediately following deregulation was also examined; this period was characterised by relatively large numbers of market entries and exits. A database was obtained from the Airports Company South Africa; air traffic movements, passenger numbers and load factors were evaluated. The study showed that the market is still characterised by regular market entries and exits. Also that the entry of the low-cost carriers has stimulated the market, resulting in increased air traffic movements, higher passenger numbers, higher load factors in general and the opening of a secondary airport in Gauteng, Lanseria International. Deregulation and, more specifically, the entry of the low-cost carriers has resulted in structural changes in the market and more choice for passengers.

  8. Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism.

    Science.gov (United States)

    Arachchillage, D R J; Mackie, I J; Efthymiou, M; Chitolie, A; Hunt, B J; Isenberg, D A; Khamashta, M; Machin, S J; Cohen, H

    2016-11-01

    Essentials Complement activation has a pathogenic role in thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Complement activation markers were elevated in anticoagulated thrombotic APS patients. Complement activation decreased in APS patients switching from warfarin to rivaroxaban. Background Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL -1 ) [confidence interval] 64 [29-125] vs. 83 [35-147], 9 [2-15] vs. 12 [4-18] and 171 [56-245] vs. 201 [66-350], respectively) but levels of Bb fragment were unchanged. There were no correlations between rivaroxaban levels and complement activation markers. Conclusions APS patients with previous VTE on warfarin exhibit increased complement activation, which is likely to occur via the classical pathway and is decreased by rivaroxaban administration

  9. MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression

    International Nuclear Information System (INIS)

    Zhong, Xiaohua; Xiao, Yipin; Chen, Chao; Wei, Xiuwen; Hu, Chen; Ling, Xukun; Liu, Xinbin

    2015-01-01

    Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR-203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment. - Highlights: • CPEB4 is aberrantly expressed in human colorectal cancers. • Knockdown of CPEB4 inhibited colorectal cancer cell proliferation and enhanced apoptosis. • CPEB4 is a direct target of miR-203 and inversely correlates with miR-203 expression. • miR-203 inhibited cell growth and enhanced cell apoptosis in CPEB4 dependent manner. • miR-203 is an upstream regulator of the CPEB4-induced apoptosis pathway.

  10. MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xiaohua; Xiao, Yipin; Chen, Chao, E-mail: chenchaopw@126.com; Wei, Xiuwen; Hu, Chen; Ling, Xukun; Liu, Xinbin

    2015-10-16

    Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR-203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment. - Highlights: • CPEB4 is aberrantly expressed in human colorectal cancers. • Knockdown of CPEB4 inhibited colorectal cancer cell proliferation and enhanced apoptosis. • CPEB4 is a direct target of miR-203 and inversely correlates with miR-203 expression. • miR-203 inhibited cell growth and enhanced cell apoptosis in CPEB4 dependent manner. • miR-203 is an upstream regulator of the CPEB4-induced apoptosis pathway.

  11. Internet-based wide area measurement applications in deregulated power systems

    Science.gov (United States)

    Khatib, Abdel-Rahman Amin

    Since the deregulation of power systems was started in 1989 in the UK, many countries have been motivated to undergo deregulation. The United State started deregulation in the energy sector in California back in 1996. Since that time many other states have also started the deregulation procedures in different utilities. Most of the deregulation market in the United States now is in the wholesale market area, however, the retail market is still undergoing changes. Deregulation has many impacts on power system network operation and control. The number of power transactions among the utilities has increased and many Independent Power Producers (IPPs) now have a rich market for competition especially in the green power market. The Federal Energy Regulatory Commission (FERC) called upon utilities to develop the Regional Transmission Organization (RTO). The RTO is a step toward the national transmission grid. RTO is an independent entity that will operate the transmission system in a large region. The main goal of forming RTOs is to increase the operation efficiency of the power network under the impact of the deregulated market. The objective of this work is to study Internet based Wide Area Information Sharing (WAIS) applications in the deregulated power system. The study is the first step toward building a national transmission grid picture using information sharing among utilities. Two main topics are covered as applications for the WAIS in the deregulated power system, state estimation and Total Transfer Capability (TTC) calculations. As a first step for building this national transmission grid picture, WAIS and the level of information sharing of the state estimation calculations have been discussed. WAIS impacts to the TTC calculations are also covered. A new technique to update the TTC using on line measurements based on WAIS created by sharing state estimation is presented.

  12. Complement propriety and conspiracy in nanomedicine

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein

    2016-01-01

    The complement system is the first line of body's defense against intruders and it acts as a functional bridge between innate and adaptive arms of the immune system. This commentary examines the key roles of complement activation in response to nanomedicine administration, including nucleic acid...... complexes. These comprise beneficial (eg, adjuvanticity) as well as adverse effects (eg, infusion-related reactions). Pigs (and sheep) are often used as predictive models of nanomedicine-mediated infusion-related reactions in humans. The validity of these models in relation to human responses is questioned...

  13. Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E

    1984-01-01

    Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease g...

  14. Aberrant Signaling Pathways in Glioma

    International Nuclear Information System (INIS)

    Nakada, Mitsutoshi; Kita, Daisuke; Watanabe, Takuya; Hayashi, Yutaka; Teng, Lei; Pyko, Ilya V.; Hamada, Jun-Ichiro

    2011-01-01

    Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies

  15. Decision modelling tools for utilities in the deregulated energy market

    Energy Technology Data Exchange (ETDEWEB)

    Makkonen, S. [Process Vision Oy, Helsinki (Finland)

    2005-07-01

    This thesis examines the impact of the deregulation of the energy market on decision making and optimisation in utilities and demonstrates how decision support applications can solve specific encountered tasks in this context. The themes of the thesis are presented in different frameworks in order to clarify the complex decision making and optimisation environment where new sources of uncertainties arise due to the convergence of energy markets, globalisation of energy business and increasing competition. This thesis reflects the changes in the decision making and planning environment of European energy companies during the period from 1995 to 2004. It also follows the development of computational performance and evolution of energy information systems during the same period. Specifically, this thesis consists of studies at several levels of the decision making hierarchy ranging from top-level strategic decision problems to specific optimisation algorithms. On the other hand, the studies also follow the progress of the liberalised energy market from the monopolistic era to the fully competitive market with new trading instruments and issues like emissions trading. This thesis suggests that there is an increasing need for optimisation and multiple criteria decision making methods, and that new approaches based on the use of operations research are welcome as the deregulation proceeds and uncertainties increase. Technically, the optimisation applications presented are based on Lagrangian relaxation techniques and the dedicated Power Simplex algorithm supplemented with stochastic scenario analysis for decision support, a heuristic method to allocate common benefits and potential losses of coalitions of power companies, and an advanced Branch- and-Bound algorithm to solve efficiently nonconvex optimisation problems. The optimisation problems are part of the operational and tactical decision making process that has become very complex in the recent years. Similarly

  16. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses.

    Directory of Open Access Journals (Sweden)

    Guido Moll

    Full Text Available Infusion of human third-party mesenchymal stromal cells (MSCs appears to be a promising therapy for acute graft-versus-host disease (aGvHD. To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46 and DAF (CD55, but were protected from complement lysis via expression of protectin (CD59. Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.

  17. Site-targeted complement inhibition by a complement receptor 2-conjugated inhibitor (mTT30) ameliorates post-injury neuropathology in mouse brains.

    Science.gov (United States)

    Rich, Megan C; Keene, Chesleigh N; Neher, Miriam D; Johnson, Krista; Yu, Zhao-Xue; Ganivet, Antoine; Holers, V Michael; Stahel, Philip F

    2016-03-23

    Intracerebral complement activation after severe traumatic brain injury (TBI) leads to a cascade of neuroinflammatory pathological sequelae that propagate host-mediated secondary brain injury and adverse outcomes. There are currently no specific pharmacological agents on the market to prevent or mitigate the development of secondary cerebral insults after TBI. A novel chimeric CR2-fH compound (mTT30) provides targeted inhibition of the alternative complement pathway at the site of tissue injury. This experimental study was designed to test the neuroprotective effects of mTT30 in a mouse model of closed head injury. The administration of 500 μg mTT30 i.v. at 1 h, 4 h and 24 h after head injury attenuated complement C3 deposition in injured brains, reduced the extent of neuronal cell death, and decreased post-injury microglial activation, compared to vehicle-injected placebo controls. These data imply that site-targeted alternative pathway complement inhibition may represent a new promising therapeutic avenue for the future management of severe TBI. Copyright © 2016. Published by Elsevier Ireland Ltd.

  18. Graphs whose complement and square are isomorphic

    DEFF Research Database (Denmark)

    Pedersen, Anders Sune

    2014-01-01

    We study square-complementary graphs, that is, graphs whose complement and square are isomorphic. We prove several necessary conditions for a graph to be square-complementary, describe ways of building new square-complementary graphs from existing ones, construct infinite families of square-compl...

  19. Association of Low Ficolin-Lectin Pathway Parameters with Cardiac Syndrome X

    DEFF Research Database (Denmark)

    Horváth, Z; Csuka, Dorottya; Vargova, K

    2016-01-01

    In patients with typical angina pectoris, inducible myocardial ischaemia and macroscopically normal coronaries (cardiac syndrome X (CSX)), a significantly elevated plasma level of terminal complement complex (TCC), the common end product of complement activation, has been observed without.......003). In conclusion, in patients with typical angina and myocardial ischaemia despite macroscopically normal coronary arteries, low levels of several lectin pathway parameters were observed, indicating complement activation and consumption. Complement activation through the ficolin-lectin pathway might play a role...

  20. Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation.

    Science.gov (United States)

    Lekowski, R; Collard, C D; Reenstra, W R; Stahl, G L

    2001-02-01

    Complement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose-binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O(2), 24 hr) significantly increased Ulex europaeus agglutinin II (UEA-II) binding by 72 +/- 9% compared to normoxic cells. UEA-II inhibited MBL binding to HUVEC in a concentration-dependent manner following oxidative stress. Further, MBL inhibited UEA-II binding to HUVEC in a concentration-dependent manner following oxidative stress, suggesting a common ligand. UEA-II (< or = 100 micromol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway-specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA-II in a concentration-dependent manner (IC(50) = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC(50) approximately 1 pmol/L). Finally, UEA-II significantly inhibited complement-dependent neutrophil chemotaxis, but failed to inhibit fMLP-mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA-II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress.

  1. The complement system: a gateway to gene-environment interactions in schizophrenia pathogenesis.

    Science.gov (United States)

    Nimgaonkar, V L; Prasad, K M; Chowdari, K V; Severance, E G; Yolken, R H

    2017-11-01

    The pathogenesis of schizophrenia is considered to be multi-factorial, with likely gene-environment interactions (GEI). Genetic and environmental risk factors are being identified with increasing frequency, yet their very number vastly increases the scope of possible GEI, making it difficult to identify them with certainty. Accumulating evidence suggests a dysregulated complement pathway among the pathogenic processes of schizophrenia. The complement pathway mediates innate and acquired immunity, and its activation drives the removal of damaged cells, autoantigens and environmentally derived antigens. Abnormalities in complement functions occur in many infectious and autoimmune disorders that have been linked to schizophrenia. Many older reports indicate altered serum complement activity in schizophrenia, though the data are inconclusive. Compellingly, recent genome-wide association studies suggest repeat polymorphisms incorporating the complement 4A (C4A) and 4B (C4B) genes as risk factors for schizophrenia. The C4A/C4B genetic associations have re-ignited interest not only in inflammation-related models for schizophrenia pathogenesis, but also in neurodevelopmental theories, because rodent models indicate a role for complement proteins in synaptic pruning and neurodevelopment. Thus, the complement system could be used as one of the 'staging posts' for a variety of focused studies of schizophrenia pathogenesis. They include GEI studies of the C4A/C4B repeat polymorphisms in relation to inflammation-related or infectious processes, animal model studies and tests of hypotheses linked to autoimmune diseases that can co-segregate with schizophrenia. If they can be replicated, such studies would vastly improve our understanding of pathogenic processes in schizophrenia through GEI analyses and open new avenues for therapy.

  2. Deregulation and competitive power markets -- Its impact on developing economies

    International Nuclear Information System (INIS)

    Saran, K.

    1998-01-01

    The aim of privatization in developed countries is to encourage competition in generation and supply of power whereas the focus of developing economies is to bridge the demand supply gap by addition of capacity. However, there needs to be a reconciliation between these two apparently having conflicting objectives even in case of developing economies. In competitive power markets it is necessary that rules of the game are identified in advance and followed uniformly by all players. Existence of a ''referee'' would be necessary to regulate the game so as to ensure fair play. The regulatory institution would serve this purpose and work as a stimulator to development of privatization and competitive power markets in developing economies. Consumer interests should be of upper-most priority in the mind while establishing power markets and regulatory institutions, particularly as market forces are unfavorable to consumer interests in power shortage conditions. As competition fosters, gradually market forces take over and the ''harsh'' regulator would convert itself to a ''silent vigil referee'' so as to ensure genuine competition. The debate of deregulation vs. regulation will continue but the show must go on for building of an increasingly sound, competitive and vibrant power sector in the interest of end use consumers. The planned and phased restructuring though a delayed process is a preferred process and India is fully determined to achieve this

  3. Reliability evaluation of deregulated electric power systems for planning applications

    International Nuclear Information System (INIS)

    Ehsani, A.; Ranjbar, A.M.; Jafari, A.; Fotuhi-Firuzabad, M.

    2008-01-01

    In a deregulated electric power utility industry in which a competitive electricity market can influence system reliability, market risks cannot be ignored. This paper (1) proposes an analytical probabilistic model for reliability evaluation of competitive electricity markets and (2) develops a methodology for incorporating the market reliability problem into HLII reliability studies. A Markov state space diagram is employed to evaluate the market reliability. Since the market is a continuously operated system, the concept of absorbing states is applied to it in order to evaluate the reliability. The market states are identified by using market performance indices and the transition rates are calculated by using historical data. The key point in the proposed method is the concept that the reliability level of a restructured electric power system can be calculated using the availability of the composite power system (HLII) and the reliability of the electricity market. Two case studies are carried out over Roy Billinton Test System (RBTS) to illustrate interesting features of the proposed methodology

  4. Commercial banking in the conditions of deregulation vs. reregulation

    Directory of Open Access Journals (Sweden)

    Zaklan Damir

    2014-01-01

    Full Text Available This paper examines contemporary trends in commercial banking, confronting the stages of deregulation and reregulation in this field triggered by the global mortgage crisis. Under deregulatory conditions the competitive position of banks has toughened, and they reacted to it by intensifying: marketization, i.e. globalization, concentration, securitization and conglomeration, and by turning to the profit-oriented risk management of their activity. The contraction of their interest margin was thus neutralized by the reduction of operational costs and loss provisions, and by an increase in non-interest revenues, thereby maintaining banking profitability. The recent crisis has pinpointed the necessity of firmer regulation or reregulation of the banking sector, aimed at reducing its systemic risk, the most important aspect of which being the stricter international banking capital and liquidity standards, along with the requirement to adequately treat systemically important banks. Reregulation should strengthen capitalization and liquidity; mitigate the volume, concentration, internationalization and business dispersion, hence improving the supervision of the banking sector, implying its lower, yet more stable profitability. Such an impact of the adopted section of targeted regulatory measures has been indicated by higher liquidity, lower globalization, slower concentration and securitization, and stabilization-oriented risk management activities of today's banks. Their growth and profitability have shrunk.

  5. Deregulation and restructuring of the electric utility industry

    Energy Technology Data Exchange (ETDEWEB)

    Nixon, Hal [Utility Workers Union of America (UWUA), AFL-CIO, (United States)

    1997-12-31

    Federal and state policy makers are currently faced with the rapidly evolving issue of the restructuring and potential deregulation of the electric utility industry, a sector of the economy of huge importance through its sheer size and its impact on the daily life and livelihood of everyone. This paper describes eleven principles that must be adhered to in any restructuring of the electric industry. Adherence to the principle and positions outlined can help assure that the transition in this industry benefits all, not just a few, and that the general health and welfare of the people is protected and enhanced [Espanol] Los legisladores estatales y federales se estan enfrentando con el rapido y envolvente aspecto de la reestructuracion y desregulacion potencial de la industria electrica, un sector de la economia de enorme importancia por su tamano y su impacto en la vida diaria y los medios de vida. En esta ponencia se describen once principios y posiciones que deben ser considerados en cualquier reestructuracion de la industria electrica. El apego a los principios y posiciones comentados puede ayudar a asegurar que la transicion en esta industria deneficie a todos, no solo a unos cuantos, y que la salud general y bienestar de la gente sea protegida y mejorada

  6. Investment and deregulation in the electricity generation industry

    International Nuclear Information System (INIS)

    Peluchon, B.

    2007-12-01

    This work addresses the issue of investment in the electricity generation industry. As the analysis of many crisis which have affected electricity markets shows, there is a systematic under-investment in peak capacity. Electricity prices are not high enough to cover fixed costs of such generators, a phenomenon that has been dubbed 'missing money' in some recent papers (Stoft). The investment decisions of a duo-poly facing random demand are then compared to those of a public monopoly. The results are that no prices may be high enough to solve the 'missing money' problem, since the duo-poly is able to exercise market power in order to maximize his profit. This results systematically in fewer peak capacity in the duo-poly case than in the public monopoly case. This remains true in the case of a n-oligopoly. The necessity of designing a mechanism remunerating capacity is thus demonstrated. Capacity markets are then analysed in the light of those results. What appears is that operating reserves are a public good and, as such, prevents capacity markets to solve the 'missing money' problem. This casts a shadow on the pursuit of deregulation in the electricity industry. (author)

  7. Deregulation - precondition for distributed energy in the economies in transition

    International Nuclear Information System (INIS)

    Brendow, K.

    2001-01-01

    This paper holds that deregulation, i.e. restructuring, competition and privatisation, is the main precondition for a more pronounced development of distributed power (DP) in the economies in transition in central and eastern Europe. This, then, raises the question how far the electricity, gas, steam and heat generating industries have presently moved on their way towards more market-oriented frameworks, competition and private ownership. A good benchmark for measuring progress is the existence (or lack thereof), and nature, of regulatory regimes enabling fair competition among large centralised and small decentralised power, and between wholesale generators and distributors on the one hand and customers or ''autoproducers'' or power merchants on the other. The paper describes the regulatory models applied or contemplated in the winter 2000/2001 in the various countries of central and eastern Europe and identifies fifteen general issues that require attention and solution. With regard to DP, it concludes that a major upswing is unlikely to occur before 2005-2008. While technological options abound, the institutional frameworks for customer-owned competitive DP systems are only being contemplated at present and only rarely put in place.(author)

  8. Opportunities for privatization and alliances in a deregulated marketplace

    Energy Technology Data Exchange (ETDEWEB)

    Erling, J.M. [KPMG, Toronto, ON (Canada)

    1998-09-01

    The main implications for municipal electric utilities (MEUs) and businesses in a deregulated, open access energy market include a range of possible alternative business structures, constraints on choices, increased risks, the need to understand objectives, capabilities and capacity for bearing risks. The issue of what business MEUs are in, what services they provide and how those services should be delivered, was hotly debated. It was suggested that with increasing competition, the range of possible business structures and arrangements will widen significantly. The different public-private options available to MEUs are (1) the conventional tender process, (2) contracting out, (3) joint ventures with a private company, (4) franchising, (5) outsourcing of specific functions, (6) operating agreements, (7) lease arrangements, (8) build-operate-transfer options (BOTs), and (9) the full privatization scenario. It was noted that some forms of public-private partnerships are more suited to some businesses than others. Also, different partnership structures can be used in different parts of any business. Objectives for any partnership should include maximizing profitability, minimizing risk and promoting economic development but under competition. The ability to choose objectives will change significantly and the achievement of any of the objectives will be determined by the marketplace. Some guidelines on measuring success and on maximizing market value were offered. Global trends towards more unbundling and price transparency, more outsourcing to the private sector, more competition, less government, regulatory reform and blurring of the boundaries between utility sectors were predicted.

  9. A multi-channel stakeholder consultation process for transmission deregulation

    International Nuclear Information System (INIS)

    Gregory, Robin; Fischhoff, Baruch; Thorne, Sarah; Butte, Gordon

    2003-01-01

    Deregulating Ontario's energy market required designing a rate structure for transmission costs that previously had been bundled with other electricity services. The Ontario Hydro Networks Company (now called Hydro One Networks, or 'Hydro One') owns and operates the transmission lines. It sought input from a full spectrum of stakeholders in preparing a proposed rate structure for submission to the regulator, the Ontario Energy Board (OEB). Securing that input meant accommodating great differences in stakeholders' familiarity with the (often highly technical) issues of rate setting. Hydro One drew on recent developments in stakeholder processes, integrated assessment, and risk communication to create a multi-channel process for eliciting and responding to stakeholder input. That process included (a) detailed background documents, (b) dedicated briefings and workshops, (c) mental models interviews, (d) focused meetings, and (e) mail (and email) boxes. The process was coordinated with a formal expert model, summarizing the factors determining the multiple impacts of the rate structure and the regulatory process producing it. The model analyzed these impacts, structured communications, and organized inputs, in a comprehensive and coherent way. This process facilitated developing proposals that were both technically sound and widely accepted by stakeholders, including the OEB. The case study provides a model for addressing other problems requiring stakeholder input on complex technical issues. It contrasts with other consultative processes with a less formal structure for eliciting concerns, less ability to encourage learning, and greater emphasis on achieving consensus

  10. Natural gas market assessment ten years after deregulation

    International Nuclear Information System (INIS)

    1996-11-01

    Changes which have taken place in the Canadian natural gas market in the ten years since the gas market was de-regulated, were reviewed. A 1985 agreement created conditions for a competitive natural gas market. However, the National Energy Board ensured that the pipeline transmission sector of the gas industry would continue to be regulated because of its natural monopoly characteristics. Open non-discriminatory access was to be provided to all shippers on inter-provincial gas pipelines. One objective of this report was to provide the Board with the means of assuring itself that the market was operating in such a way that Canadian requirements for natural gas were being met at fair market prices. The report also provided a review of the major changes in the gas producing and transmission sector, and reviewed developments in gas markets and sales practices. The overall assessment was that the natural gas industry was efficient and responsive to the demands of the marketplace. 5 tabs., 30 figs

  11. Global implications of U.S. power deregulation

    International Nuclear Information System (INIS)

    Maschoff, D.C.

    1996-01-01

    With U.S. power deregulation remaining a topic that is dominating the entire North American energy marketplace, this paper provides an update of events occurring in U.S. electric power markets, offering some observations about changes due to increasing competition in electric power markets, and discusses some reasons why the events in U.S. electric power markets will soon transform global energy markets. How quickly is the move from local service territory to global markets proceeding? More than fifty U.S. utility companies with revenues of over $1 billion (U.S.) will soon be actively seeking and participating in global business opportunities. Using the same logic that led them to pursue utility initiatives nationally, U.S. utilities will use their core capabilities to compete in global energy services markets. In connection with these global initiatives, U.S. utilities will bring the same fuel-neutral, gas-electric perspective to international electric power and natural gas markets. (Author)

  12. Deregulation in the electricity sector: Understanding strategic and regulatory risk

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, E.R. [City Univ. Business School, Dept. Management Systems and Information, London (United Kingdom); Bunn, D.W. [London Business School, London (United Kingdom)

    1999-08-01

    This paper is motivated by our experiences since 1990 with developing system simulation models to help UK companies in the restructured electricity industry understand the radically different market within which they must become competitive. When public utilities such as electricity have been restructured, deregulated and/or privatised, the process has often been associated with a major change in the competitive environment. As a consequence, the strategic and regulatory uncertainties ahead for these companies are unprecedented. In such a market there has been no historical evolution and all the participants including the regulatory institutions have very little understanding of how it will operate in the short term and evolve in the future. In this situation, the use of systems dynamic models appears to offer an attractive way of gaining insights into how aspects of the competitive market might evolve. In the absence of real experience and relevant analogies, learning from models assumes a key role. Such models cannot be validated empirically, but can be developed to represent how the system is designed to operate. From such a prototypical basis, sensitivity analysis can generate insights on the strategic opportunities created failings in the market design, or its potential instability to shocks and market imperfections. (au)

  13. Price-elastic demand in deregulated electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Siddiqui, Afzal S.

    2003-05-01

    The degree to which any deregulated market functions efficiently often depends on the ability of market agents to respond quickly to fluctuating conditions. Many restructured electricity markets, however, experience high prices caused by supply shortages and little demand-side response. We examine the implications for market operations when a risk-averse retailer's end-use consumers are allowed to perceive real-time variations in the electricity spot price. Using a market-equilibrium model, we find that price elasticity both increases the retailers revenue risk exposure and decreases the spot price. Since the latter induces the retailer to reduce forward electricity purchases, while the former has the opposite effect, the overall impact of price responsive demand on the relative magnitudes of its risk exposure and end-user price elasticity. Nevertheless, price elasticity decreases cumulative electricity consumption. By extending the analysis to allow for early settlement of demand, we find that forward stage end-user price responsiveness decreases the electricity forward price relative to the case with price-elastic demand only in real time. Moreover, we find that only if forward stage end-user demand is price elastic will the equilibrium electricity forward price be reduced.

  14. FACTS controllers and the deregulated electric utility environment

    International Nuclear Information System (INIS)

    Ooi, B. T.; Galiana, F. D.; McGillis, D.; Joos, G.; Marceau, R.

    1998-01-01

    The concept of Flexible AC Transmission Systems (FACTS) is explored and the potential of power electronic converters to increase flexibility and reliability of modern power systems is explored. Power electronic controllers can reduce the required safety margin in electric power generation capacity through the use of faster controllers based on exploiting the high-power solid-state switches with gate-turn-off capabilities. The FACTS concept makes it possible to postpone the financial investment needed to build more power lines, and also offers a solution to securing the right-of-way to build new lines. Currently available FACTS controllers such as the Static var Compensator (STATCOM) and the Unified Power Flow Controller (UPFC) are described, including their function, structure and relevant implementation issues. Since they can produce the required amount of reactive power independently of line voltage or current, and if equipped with energy storing devices they can supply real power as required, they are a necessary element for the control of power systems in a deregulated environment. 15 refs., 3 figs

  15. Complement-related proteins control the flavivirus infection of Aedes aegypti by inducing antimicrobial peptides.

    Directory of Open Access Journals (Sweden)

    Xiaoping Xiao

    2014-04-01

    Full Text Available The complement system functions during the early phase of infection and directly mediates pathogen elimination. The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism. Thioester (TE-containing proteins (TEPs, which show high similarity to mammalian complement C3, are thought to play a key role in innate immunity in arthropods. Herein, we report that a viral recognition cascade composed of two complement-related proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti macroglobulin complement-related factor (AaMCR, belonging to the insect TEP family, is a crucial effector in opposing the flaviviral infection of A. aegypti. However, AaMCR does not directly interact with DENV, and its antiviral effect requires an A. aegypti homologue of scavenger receptor-C (AaSR-C, which interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore, recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of antimicrobial peptides (AMPs, which exerts potent anti-DENV activity. Our results both demonstrate the existence of a viral recognition pathway that controls the flaviviral infection by inducing AMPs and offer insights into a previously unappreciated antiviral function of the complement-like system in arthropods.

  16. Identification of the Fanconi Anemia Complementation Group I Gene, FANCI

    Directory of Open Access Journals (Sweden)

    Josephine C. Dorsman

    2007-01-01

    Full Text Available To identify the gene underlying Fanconi anemia (FA complementation group I we studied informative FA-I families by a genome-wide linkage analysis, which resulted in 4 candidate regions together encompassing 351 genes. Candidates were selected via bioinformatics and data mining on the basis of their resemblance to other FA genes/proteins acting in the FA pathway, such as: degree of evolutionary conservation, presence of nuclear localization signals and pattern of tissue-dependent expression. We found a candidate, KIAA1794 on chromosome 15q25-26, to be mutated in 8 affected individuals previously assigned to complementation group I. Western blots of endogenous FANCI indicated that functionally active KIAA1794 protein is lacking in FA-I individuals. Knock-down of KIAA1794 expression by siRNA in HeLa cells caused excessive chromosomal breakage induced by mitomycin C, a hallmark of FA cells. Furthermore, phenotypic reversion of a patient-derived cell line was associated with a secondary genetic alteration at the KIAA1794 locus. These data add up to two conclusions. First, KIAA1794 is a FA gene. Second, this gene is identical to FANCI, since the patient cell lines found mutated in this study included the reference cell line for group I, EUFA592.

  17. Coordinated Expression of Borrelia burgdorferi Complement Regulator-Acquiring Surface Proteins during the Lyme Disease Spirochete's Mammal-Tick Infection Cycle▿

    OpenAIRE

    Bykowski, Tomasz; Woodman, Michael E.; Cooley, Anne E.; Brissette, Catherine A.; Brade, Volker; Wallich, Reinhard; Kraiczy, Peter; Stevenson, Brian

    2007-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, is largely resistant to being killed by its hosts’ alternative complement activation pathway. One possible resistance mechanism of these bacteria is to coat their surfaces with host complement regulators, such as factor H. Five different B. burgdorferi outer surface proteins having affinities for factor H have been identified: complement regulator-acquiring surface protein 1 (BbCRASP-1), encoded by cspA; BbCRASP-2, encoded by cspZ; and three ...

  18. Cell cycle deregulation by the HBx protein of hepatitis B virus

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2007-02-01

    Full Text Available

    Cell cycle control by oncogenic viruses usually involves disruption of the normal restraints on cellular proliferation via abnormal proteolytic degradation and malignant transformation of cells. The cell cycle regulatory molecules viz. cyclins, cyclin-dependent kinases (cdks and inhibitors of cdks as well as the transcriptional targets of signaling pathways induce cells to move through the cell cycle checkpoints. These check points are often found deregulated in tumor cells and in the cells afflicted with DNA tumor viruses predisposing them towards transformation. The X protein or HBx of hepatitis B virus is a promiscuous transactivator that has been implicated in the development of hepatocellular carcinoma in humans. However, the exact role of HBx in establishing a permissive environment for hepatocarcinogenesis is not fully understood. HBx activates the Ras-Raf-MAP kinase signaling cascade, through which it activates transcription factors AP-1 and NFkappa B, and stimulates cell DNA synthesis. HBx shows a profound effect on cell cycle progression even in the absence of serum. It can override the replicative senescence of cells in G0 phase by binding to p55sen. It stimulates the G0 cells to transit through G1 phase by activating Src kinases and the cyclin A-cyclin-dependent kinase 2 complexes, that in turn induces the cyclin A promoter. There is an early and sustained level of cyclin-cdk2 complex in the presence of HBx during the cell cycle which is coupled with an increased protein kinase activity of cdk2 suggesting an early appearance of S phase. The interaction between cyclin-cdk2 complex and HBx occurs through its carboxyterminal region (amino acids 85-119 and requires a constitutive Src kinase activity. The increased cdk2 activity is associated with stabilization of cyclin E as well as proteasomal degradation of cdk inhibitor p27Kip1. Notably, the HBx mutant

  19. Effects of the Deregulation on the Concentration of the Brazilian Air Transportation Industry

    Science.gov (United States)

    Guterres, Marcelo Xavier; Muller, Carlos

    2003-01-01

    This paper addresses the effects of the deregulation of the Brazilian air transportation industry in terms of the concentration of the market. We will show some metrics that are commonly used to study the concentration of the industry. This paper uses the Herfindhal- Hirschman Index. This index tends to zero in the competitive scenario, with a large number of small firms, and to one in case of a monopolistic scenario. The paper analyses the dynamics of the concentration of the Brazilian domestic air transportation market, in order to evaluate the effects of deregulation. We conclude that the Brazilian market presents oligopoly characteristics and aspects in its current structure that maintain the market concentrated in spite of the Deregulation measures adopted by the aeronautical authority. Keywords: Herfindhal-Hirschman Index, concentration, Deregulation

  20. TCSC based automatic generation control of deregulated power system using quasi-oppositional harmony search algorithm

    Directory of Open Access Journals (Sweden)

    Mahendra Nandi

    2017-08-01

    Full Text Available In present aspect, automatic generation control (AGC of deregulated power system with thyristor controlled series compensator (TCSC device is investigated. The objective is to discuss bilateral power transaction issue with the TCSC effect. A deregulated two-area power system model having two thermal units in each control area is considered for this act. A quasi-oppositional harmony search (QOHS algorithm is being applied for the constrained optimization problem. Three cases, commonly studied in deregulation, are discussed for the effectiveness of the proposed technique. Further, sensitivity analysis is studied by varying the test system parameters up to ±25% from their rated values. The obtained simulation plots are analytically discussed with the calculation of oscillatory modes, transient details and the studied performance indices. Sugeno fuzzy logic control technique is also investigated to the studied test system. The simulation results show that the proposed QOHS based TCSC controller is quite effective in deregulated environment.

  1. Regulatory Assessment of the Effects of Economic Deregulation of the Nuclear Industry

    International Nuclear Information System (INIS)

    2002-11-01

    The European Commission Nuclear Regulators Working Group (NRWG) appointed a Task Force (TF) to develop a common view among European regulators on the assessment of typical safety consequences resulting from economic pressure on operators as a result of deregulation of electricity markets. Although the report seems to imply that there are only negative aspects of deregulation, this is not the case. As the focus of the TF has been potential safety consequences we have not dealt with potential positive effects of deregulation. To provide a general background to the analyses of the safety consequences, the TF undertook a survey of the current situation within the EU and candidate countries on aspects of economic deregulation of the countries nuclear industry and the experiences so far of regulating these issues. Answers were submitted in of July 2001. 13 NRWG members with nuclear power plants took part in the survey. (author)

  2. The limits to deregulation of entry and expansion of the US gas pipeline industry

    International Nuclear Information System (INIS)

    Rosput, P.G.

    1993-01-01

    US consumers of natural gas have enjoyed significant benefits as the pricing of the commodity has been deregulated. Thanks in large part to the success of deregulation of the natural gas commodity. US federal regulators have embarked upon a wide-ranging programme of eliminating barriers to entry and expansion of natural gas pipelines, which have traditionally been regulated as natural monopolies. As a result, there is now significant excess capacity in the natural gas transmission sector, without measurable benefits to consumers. (author)

  3. Market Power of Local Cable Television Franchises: Evidence from the Effects of Deregulation

    OpenAIRE

    Adam B. Jaffe; David M. Kanter

    1990-01-01

    The 1989 Cable Act eliminated most price regulation of cable television operators, including the right of municipalities to enforce price terms in franchise agreements. Deregulation was justified, at least partially, by the contention that competition from other entertainment media eliminated any market power of cable franchises. We examine the value at sale of existing cable systems before and after deregulation. Assuming that this value represents the expected present value of future profit...

  4. The Importance of Management in the Deregulated Retail Electricity Distribution Market in Slovenia

    OpenAIRE

    Drago Papler; Stefan Bojnec

    2006-01-01

    This paper underlines the importance of management in the deregulated retail electricity distribution market, entrepreneurship and business behaviours toward consumers’ satisfaction with quality of services. The coefficients of concentration indicate a high concentration of electricity suppliers and users in the deregulated electricity retail market for industry. The production function reveals the importance of education and electricity infrastructure, and to a lesser extent of capital inten...

  5. DAIRY DEREGULATION AND LOW-INPUT DAIRY PRODUCTION: A BIOECONOMIC EVALUATION

    OpenAIRE

    Tozer, Peter R.; Huffaker, Ray G.

    1999-01-01

    Deregulation of the Australian dairy industry could affect the utilization of resources by milk producers and the profitability of dairy production. In this study we examine the feed mix that dairy producers use, both pastures and supplements, under partial and total deregulation. We are particularly interested in the interaction of pasture utilization and farm profitability. The results of this research demonstrate that profitable low-input dairy is constrained by the most limiting resource,...

  6. Assessing the Significance of Telecommunication Deregulation on the Growth of Japan's Mobile Phone Market

    OpenAIRE

    Yuqing Xing

    2001-01-01

    This paper analyzes the development of Japan's mobile phone market. Specifically, it focuses on the regulatory reforms of Japan's mobile communication sector and their impact on the growth of the market. The analysis based on a monopolistic competition model shows that the deregulation policies perform an essential role in fostering the rapid expansion of Japan's mobile phone market. Using quarterly data from 1991 to 1999, the paper tests the significance of the telecommunication deregulation...

  7. Incident microalbuminuria and complement factor mannan-binding lectin-associated protein 19 in people with newly diagnosed type 1 diabetes

    DEFF Research Database (Denmark)

    Ostergaard, J A; Thiel, S; Hoffmann-Petersen, I T

    2017-01-01

    BACKGROUND: Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, e.g., mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The ...

  8. Tumour exosomes display different differential mechanical and complement activation properties dependent on malignant state: implications in endothelial leakiness

    DEFF Research Database (Denmark)

    Whitehead, Bradley Joseph; Wu, Linping; Hvam, Michael Lykke

    2015-01-01

    (QNM AFM) to determine size and nanomechanical properties. Effect of HCV-29, T24 and FL3 exosomes on human umbilical vein endothelial cell (HUVEC) monolayer integrity was determined by transendothelial electrical resistance (TEER) measurements and transport was determined by flow cytometry. Complement......). Malignant cell-derived exosomes activated complement through calcium-sensitive pathways in a concentration-dependent manner. Conclusions : Malignant (metastatic and non-metastatic) cell line exosomes display a markedly reduced stiffness and adhesion but an increased complement activation compared to non...

  9. PO-20 - Crosstalk between the lectin pathway and haemostasis in patients with pulmonary cancer

    DEFF Research Database (Denmark)

    Larsen, J B; Christensen, T D; Hvas, C L

    2016-01-01

    INTRODUCTION: Recent research has focused on the complement system in cancer, including the lectin pathway of complement activation. Mannose-binding lectin (MBL), a key activator of the lectin pathway, can bind to tumor cell surfaces in vitro, and lectin pathway activation is increased in several...

  10. DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

    Directory of Open Access Journals (Sweden)

    John Paul SanGiovanni

    Full Text Available Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs and use of peroxisome proliferator activator receptor (PPAR-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG co-activator 1 alpha (PPARGC1A, a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR transcription complex, may influence neovascularization (NV in age-related macular degeneration (AMD.We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A.A DNA coding variant (rs3736265 and a 3'UTR-resident regulatory variant (rs3774923 in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs. SNP-SNP interactions existed for NV AMD (P<0.005 with rs3736265 and a AMD-associated variant in complement factor B (CFB, rs512559. PPARGC1A influences activation of the AMD-associated complement component 3 (C3 promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P ≤ 0.003 of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033, a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678 showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P ≤ 0.003. C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice

  11. complement C3, Complement C4 and C-reactive protein

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... (IL-6), E-selectin and P-selectin (Perlstein and Lee,. 2006). Studies have ... of cigarette smoke causes complement activation which is in turn ..... are decreased by long term smoking cessation in male smokers. Prevent. Med.

  12. Different host complement systems and their interactions with saliva from Lutzomyia longipalpis (Diptera, Psychodidae and Leishmania infantum promastigotes.

    Directory of Open Access Journals (Sweden)

    Antonio Ferreira Mendes-Sousa

    Full Text Available BACKGROUND: Lutzomyia longipalpis is the vector of Leishmania infantum in the New World, and its saliva inhibits classical and alternative human complement system pathways. This inhibition is important in protecting the insect´s midgut from damage by the complement. L. longipalpis is a promiscuous blood feeder and must be protected against its host's complement. The objective of this study was to investigate the action of salivary complement inhibitors on the sera of different host species, such as dogs, guinea pigs, rats and chickens, at a pH of 7.4 (normal blood pH and 8.15 (the midgut pH immediately after a blood meal. We also investigated the role of the chicken complement system in Leishmania clearance in the presence and absence of vector saliva. RESULTS: The saliva was capable of inhibiting classical pathways in dogs, guinea pigs and rats at both pHs. The alternative pathway was not inhibited except in dogs at a pH of 8.15. The chicken classical pathway was inhibited only by high concentrations of saliva and it was better inhibited by the midgut contents of sand flies. Neither the saliva nor the midgut contents had any effect on the avian alternative pathway. Fowl sera killed L. infantum promastigotes, even at a low concentration (2%, and the addition of L. longipalpis saliva did not protect the parasites. The high body temperature of chickens (40°C had no effect on Leishmania viability during our assays. CONCLUSION: Salivary inhibitors act in a species-specific manner. It is important to determine their effects in the natural hosts of Leishmania infantum because they act on canid and rodent complements but not on chickens (which do not harbour the parasite. Moreover, we concluded that the avian complement system is the probable mechanism through which chickens eliminate Leishmania and that their high body temperature does not influence this parasite.

  13. Different host complement systems and their interactions with saliva from Lutzomyia longipalpis (Diptera, Psychodidae) and Leishmania infantum promastigotes.

    Science.gov (United States)

    Mendes-Sousa, Antonio Ferreira; Nascimento, Alexandre Alves Sousa; Queiroz, Daniel Costa; Vale, Vladimir Fazito; Fujiwara, Ricardo Toshio; Araújo, Ricardo Nascimento; Pereira, Marcos Horácio; Gontijo, Nelder Figueiredo

    2013-01-01

    Lutzomyia longipalpis is the vector of Leishmania infantum in the New World, and its saliva inhibits classical and alternative human complement system pathways. This inhibition is important in protecting the insect´s midgut from damage by the complement. L. longipalpis is a promiscuous blood feeder and must be protected against its host's complement. The objective of this study was to investigate the action of salivary complement inhibitors on the sera of different host species, such as dogs, guinea pigs, rats and chickens, at a pH of 7.4 (normal blood pH) and 8.15 (the midgut pH immediately after a blood meal). We also investigated the role of the chicken complement system in Leishmania clearance in the presence and absence of vector saliva. The saliva was capable of inhibiting classical pathways in dogs, guinea pigs and rats at both pHs. The alternative pathway was not inhibited except in dogs at a pH of 8.15. The chicken classical pathway was inhibited only by high concentrations of saliva and it was better inhibited by the midgut contents of sand flies. Neither the saliva nor the midgut contents had any effect on the avian alternative pathway. Fowl sera killed L. infantum promastigotes, even at a low concentration (2%), and the addition of L. longipalpis saliva did not protect the parasites. The high body temperature of chickens (40°C) had no effect on Leishmania viability during our assays. Salivary inhibitors act in a species-specific manner. It is important to determine their effects in the natural hosts of Leishmania infantum because they act on canid and rodent complements but not on chickens (which do not harbour the parasite). Moreover, we concluded that the avian complement system is the probable mechanism through which chickens eliminate Leishmania and that their high body temperature does not influence this parasite.

  14. Complementation analysis of ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Jaspers, N.G.; Painter, R.B.; Paterson, M.C.; Kidson, C.; Inoue, T.

    1985-01-01

    In a number of laboratories genetic analysis of ataxia-telangiectasia (AT) has been performed by studying the expression of the AT phenotype in fused somatic cells or mixtures of cell-free extracts from different patients. Complementation of the defective response to ionizing radiation was observed frequently, considering four different parameters for radiosensitivity in AT. The combined results from studies on cultured fibroblasts or lymphoblastoid cells from 17 unrelated families revealed the presence of at least four and possibly nine complementation groups. These findings suggest that there is an extensive genetic heterogeneity in AT. More extensive studies are needed for an integration of these data and to provide a set of genetically characterized cell strains for future research of the AT genetic defect

  15. The paralogous salivary anti-complement proteins IRAC I and IRAC II encoded by Ixodes ricinus ticks have broad and complementary inhibitory activities against the complement of different host species.

    Science.gov (United States)

    Schroeder, Hélène; Daix, Virginie; Gillet, Laurent; Renauld, Jean-Christophe; Vanderplasschen, Alain

    2007-02-01

    Several observations suggest that inhibition of the host complement alternative pathway by Ixodes tick saliva is crucial to achieve blood feeding. We recently described two paralogous anti-complement proteins called Ixodes ricinus anti-complement (IRAC) proteins I and II co-expressed in I. ricinus salivary glands. Phylogenetic analyses suggested that these sequences were diversifying by a process of positive Darwinian selection, possibly leading to molecules with different biological properties. In the present study, we tested the hypothesis that each paralogue may have different inhibitory activities against the complement of different natural host species, thereby contributing to broaden the host range of I. ricinus ticks. IRAC I and IRAC II were tested against the complement of eight I. ricinus natural host species (six mammals and two birds). The results demonstrate that IRAC I and IRAC II have broad and complementary inhibition activities against the complement of different host species. This report is the first description of paralogous anti-complement molecules encoded by a pathogen with broad and complementary inhibitory activities against the complement of different host species.

  16. Protecting consumer interests in Alberta's deregulated electricity market

    International Nuclear Information System (INIS)

    Bradford, J.A.

    2003-01-01

    This paper explains why the province of Alberta decided to deregulate its electricity sector. In the early 1990s, electricity rates were reasonable in Alberta, there was no utility debt, and electricity costs were low. In 1994 California's open access transmission system suggested that open markets would result in lower electricity rates and attract new economic activity. The government of Alberta also believed that competitive markets would set prices with no need for economic regulation. In the initial transition to competition, regulated electricity rates were offered to customers who were not ready to switch to the new competitive market. The RRO rate was set by the Alberta Energy and Utilities Board (EUB). The rates included the forecasted cost of purchasing energy from markets, cost of system access, and retail service costs. The end of the RRO rate was scheduled for 2005 when the market was expected be well developed. This paper also describes other protection mechanisms for consumers. Alberta's new electricity policy (NEP) eliminates generator participant costs related to transmission. EUB's zonal interconnection charges are also overruled along with the EUB-approved 50/50 division of transmission costs. Under the NEP, the ISO is to build transmission in anticipation of new generation. Consumers will fund the total cost to build new transmission capacity for exports and imports. This new transmission policy is a complete change from the original government policy which allocated some transmission costs to generators. The sudden change in policy was due to pressure from oil sands producers and oil sands co-generation developers. The claimed benefit to Albertans is a 25 per cent reduction in pool price and greater system reliability. However, the author cautioned that government interference with competitive electricity markets will cripple the electric power industry in the foreseeable future because it interferes with market prices

  17. The deregulation connection : utility competition creates new niche company

    International Nuclear Information System (INIS)

    Roy, C.

    1999-01-01

    Deregulation in Ontario's utility market has created incentives for local utilities to add new services to attract and keep customers, knowing that in a competitive energy market, only those utilities which offer the best services will survive. London Hydro, which provides power to southwestern Ontario launched a private enterprise called LondonConnect Inc. The new enterprise offers high-speed digital services to area businesses. London Hydro made this unique move to take advantage of the fact that 20 per cent of businesses communicate electronically. London Hydro believes that in the next five years, that number will increase to 80 per cent. The Metropolitan Area Network (MAN) gives businesses greater connectivity to the Internet and web services. One of the network's capabilities is realtime video conferencing between hydro locations. MAN can also be used to create a secure and private virtual community-wide area network of computers and office machines. The advantages are numerous. For example, hospitals will be able to exchange information between remote sites at incredible speeds. MAN is made up of fiber-optic cables and electronic routers. LondonConnect is expecting to provide access throughout London by the fall of 1999. A dozen clients have already signed up for the service. Installation of the system will cost $1,000 with fixed monthly rates. The cost will vary depending on the level of service. The network will cost London Hydro $3 million, but it is expected to generate $2.5 million annually in its first two years. 3 figs

  18. Deregulated Renal Calcium and Phosphate Transport during Experimental Kidney Failure.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD, yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca(2+ and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca(2+ excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-αklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal αklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp27b1, but not Cyp24a1, and blood levels of 1,25-dihydroxy vitamin D3 were significantly elevated in both models. Furthermore, kidney failure was characterized by enhanced renal expression of the transient receptor potential cation channel subfamily V member 5 (TRPV5, calbindin-D28k, and sodium-dependent Pi transporter type 2b (NaPi2b, whereas the renal expression of sodium-dependent Pi transporter type 2a (NaPi2a and type 3 (PIT2 were reduced. Together, our data indicates two different models of experimental kidney failure comparably associate with disturbed FGF23-αklotho-vitamin-D signalling and a deregulated electrolyte homeostasis. Moreover, this study identifies local tubular, possibly inflammation- or PTH- and/or FGF23-associated, adaptive mechanisms, impacting on Ca(2+/Pi homeostasis, hence enabling new opportunities to target electrolyte disturbances that emerge as a consequence of CKD development.

  19. The deregulation connection : utility competition creates new niche company

    Energy Technology Data Exchange (ETDEWEB)

    Roy, C

    1999-08-01

    Deregulation in Ontario's utility market has created incentives for local utilities to add new services to attract and keep customers, knowing that in a competitive energy market, only those utilities which offer the best services will survive. London Hydro, which provides power to southwestern Ontario launched a private enterprise called LondonConnect Inc. The new enterprise offers high-speed digital services to area businesses. London Hydro made this unique move to take advantage of the fact that 20 per cent of businesses communicate electronically. London Hydro believes that in the next five years, that number will increase to 80 per cent. The Metropolitan Area Network (MAN) gives businesses greater connectivity to the Internet and web services. One of the network's capabilities is realtime video conferencing between hydro locations. MAN can also be used to create a secure and private virtual community-wide area network of computers and office machines. The advantages are numerous. For example, hospitals will be able to exchange information between remote sites at incredible speeds. MAN is made up of fiber-optic cables and electronic routers. LondonConnect is expecting to provide access throughout London by the fall of 1999. A dozen clients have already signed up for the service. Installation of the system will cost $1,000 with fixed monthly rates. The cost will vary depending on the level of service. The network will cost London Hydro $3 million, but it is expected to generate $2.5 million annually in its first two years. 3 figs.

  20. The deregulation connection : utility competition creates new niche company

    Energy Technology Data Exchange (ETDEWEB)

    Roy, C.

    1999-08-01

    Deregulation in Ontario`s utility market has created incentives for local utilities to add new services to attract and keep customers, knowing that in a competitive energy market, only those utilities which offer the best services will survive. London Hydro, which provides power to southwestern Ontario launched a private enterprise called LondonConnect Inc. The new enterprise offers high-speed digital services to area businesses. London Hydro made this unique move to take advantage of the fact that 20 per cent of businesses communicate electronically. London Hydro believes that in the next five years, that number will increase to 80 per cent. The Metropolitan Area Network (MAN) gives businesses greater connectivity to the Internet and web services. One of the network`s capabilities is realtime video conferencing between hydro locations. MAN can also be used to create a secure and private virtual community-wide area network of computers and office machines. The advantages are numerous. For example, hospitals will be able to exchange information between remote sites at incredible speeds. MAN is made up of fiber-optic cables and electronic routers. LondonConnect is expecting to provide access throughout London by the fall of 1999. A dozen clients have already signed up for the service. Installation of the system will cost $1,000 with fixed monthly rates. The cost will vary depending on the level of service. The network will cost London Hydro $3 million, but it is expected to generate $2.5 million annually in its first two years. 3 figs.

  1. Deregulation led to record-breaking profit for SPP

    International Nuclear Information System (INIS)

    Janoska, J.

    2004-01-01

    The state collected close to 15 bn Sk of SPP's last year profits. The income tax represents about 5,2 bn Sk and the dividends paid to state as owner of 51 percent of the stock of Slovensky plynarensky priemysel, a.s., Bratislava (SPP) amount up to 9,5 billion Sk. Investors Ruhrgas and Gaz de France will split 9 billion Sk. This was possible thank to a record-breaking net profit of 20.5 billion Sk made by the company due to deregulation of the distorted gas prices for consumers that lead to an average price increase by over 30 percent. A positive impact on the company's economy had also the dissolving of provisions and reserves but on the other hand the sales went down by close to 5 percent due to higher temperatures. Another factor that had a positive impact on the company revenues was the increase of gas volumes transported through the SPP network to Western Europe. Expenditures related to purchase of gas increased last year and not even the decrease USD exchange rates could eliminate the impact of increasing gas prices. The decrease of sales on the domestic market was one of the major factors that allowed the total cost to decrease on year-to-year basis by ten percent. A restructuring of SPP should bring along further savings but the company has not calculated the total effect of a restructuring yet. The strong positive impact the restructuring may have on the company should show in 2004 and later. Last year the company concentrated on savings in area of maintenance and repairs and this year it should be the procurement expenditures that should be decreased. The future economic result of the company would depend on several factors like exchange rates, sale volumes and price of natural gas. Oils prices have reached their new maximums and the gas prices, in general, follow the oil price

  2. Complementing the sugar code: role of GAGs and sialic acid in complement regulation

    Directory of Open Access Journals (Sweden)

    Alex eLangford-Smith

    2015-02-01

    Full Text Available Sugar molecules play a vital role on both microbial and mammalian cells, where they are involved in cellular communication, govern microbial virulence and modulate host immunity and inflammatory responses. The complement cascade, as part of a host’s innate immune system, is a potent weapon against invading bacteria but has to be tightly regulated to prevent inappropriate attack and damage to host tissues. A number of complement regulators, such as factor H and properdin, interact with sugar molecules, such as glycosaminoglycans and sialic acid, on host and pathogen membranes and direct the appropriate complement response by either promoting the binding of complement activators or inhibitors. The binding of these complement regulators to sugar molecules can vary from location to location, due to their different specificities and because distinct structural and functional subpopulations of sugars are found in different human organs, such as the brain, kidney and eye. This review will cover recent studies that have provided important new insights into the role of glycosaminoglycans and sialic acid in complement regulation and how sugar recognition may be compromised in disease

  3. Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

    Directory of Open Access Journals (Sweden)

    Anna E. Maciag

    2013-01-01

    Full Text Available JS-K is a nitric oxide (NO-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

  4. Characterization of the third component of complement (C3) after activation by cigarette smoke

    International Nuclear Information System (INIS)

    Kew, R.R.; Ghebrehiwet, B.; Janoff, A.

    1987-01-01

    Activation of lung complement by tobacco smoke may be an important pathogenetic factor in the development of pulmonary emphysema in smokers. We previously showed that cigarette smoke can modify C3 and activate the alternative pathway of complement in vitro. However, the mechanism of C3 activation was not fully delineated in these earlier studies. In the present report, we show that smoke-treated C3 induces cleavage of the alternative pathway protein, Factor B, when added to serum containing Mg-EGTA. This effect of cigarette smoke is specific for C3 since smoke-treated C4, when added to Mg-EGTA-treated serum, fails to activate the alternative pathway and fails to induce Factor B cleavage. Smoke-modified C3 no longer binds significant amounts of [ 14 C]methylamine (as does native C3), and relatively little [ 14 C]methylamine is incorporated into its alpha-chain. Thus, prior internal thiolester bond cleavage appears to have occurred in C3 activated by cigarette smoke. Cigarette smoke components also induce formation of noncovalently associated, soluble C3 multimers, with a Mr ranging from 1 to 10 million. However, prior cleavage of the thiolester bond in C3 with methylamine prevents the subsequent formation of these smoke-induced aggregates. These data indicate that cigarette smoke activates the alternative pathway of complement by specifically modifying C3 and that these modifications include cleavage of the thiolester bond in C3 and formation of noncovalently linked C3 multimers

  5. The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation

    DEFF Research Database (Denmark)

    Kozarcanin, H; Lood, C; Fog, Lea Munthe

    2016-01-01

    by AT during clotting without the assistance of heparin. In all other cases the MASPs were, as previously reported, inactivated by C1-INH. In systemic lupus erythematosus patients with thrombotic disease and in polytrauma patients, the levels of activated MASP-1 and MASP-2 in complex with both AT and C1-INH...

  6. Change in consumer sensitivity to electricity prices in response to retail deregulation: A panel empirical analysis of the residential demand for electricity in the United States

    International Nuclear Information System (INIS)

    Nakajima, Tadahiro; Hamori, Shigeyuki

    2010-01-01

    About ten years have passed since the deregulation of the U.S. retail electricity market, and it is now generally accepted that the available data is adequate to quantitatively assess and compare conditions before and after deregulation. This study, therefore, estimates the changes in price elasticity in the residential electricity market to examine the changes, if any, in household sensitivity (as a result of retail electricity market deregulation policies) to residential electricity rates. Specifically, six types of panel data are prepared, based on three cross-sections-all states (except for Alaska and Hawaii) and the District of Columbia, deregulated states, and non-deregulated states-and two time series-the period before deregulation and the period after deregulation. The panel empirical analysis techniques are used to determine whether or not the variables are stationary, and to estimate price elasticity. We find that there is no substantial difference in the price elasticity between deregulated and non-deregulated states for both periods-before deregulation and after deregulation. Thus, it can be said that the deregulation of the retail electricity market has not made consumers more sensitive to electricity rates and that retail deregulation policies are not the cause of price elasticity differences between deregulated and non-deregulated states.

  7. Change in consumer sensitivity to electricity prices in response to retail deregulation. A panel empirical analysis of the residential demand for electricity in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Tadahiro [The Kansai Electric Power Company, Incorporated, 6-16, Nakanoshima 3-chome, Kita-Ku, Osaka 530-8270 (Japan); Hamori, Shigeyuki [Faculty of Economics, Kobe University 2-1, Rokkodai, Nada-Ku, Kobe 657-8501 (Japan)

    2010-05-15

    About ten years have passed since the deregulation of the U.S. retail electricity market, and it is now generally accepted that the available data is adequate to quantitatively assess and compare conditions before and after deregulation. This study, therefore, estimates the changes in price elasticity in the residential electricity market to examine the changes, if any, in household sensitivity (as a result of retail electricity market deregulation policies) to residential electricity rates. Specifically, six types of panel data are prepared, based on three cross-sections - all states (except for Alaska and Hawaii) and the District of Columbia, deregulated states, and non-deregulated states - and two time series - the period before deregulation and the period after deregulation. The panel empirical analysis techniques are used to determine whether or not the variables are stationary, and to estimate price elasticity. We find that there is no substantial difference in the price elasticity between deregulated and non-deregulated states for both periods - before deregulation and after deregulation. Thus, it can be said that the deregulation of the retail electricity market has not made consumers more sensitive to electricity rates and that retail deregulation policies are not the cause of price elasticity differences between deregulated and non-deregulated states. (author)

  8. Complement-mediated neutralization of dengue virus requires mannose-binding lectin

    DEFF Research Database (Denmark)

    Avirutnan, Panisadee; Hauhart, Richard E; Marovich, Mary A

    2011-01-01

    -dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains...... with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. IMPORTANCE Dengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue...... hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation...

  9. Genome Mining of the Marine Actinomycete Streptomyces sp. DUT11 and Discovery of Tunicamycins as Anti-complement Agents

    Directory of Open Access Journals (Sweden)

    Xiao-Na Xu

    2018-06-01

    Full Text Available Marine actinobacteria are potential producers of various secondary metabolites with diverse bioactivities. Among various bioactive compounds, anti-complement agents have received great interest for drug discovery to treat numerous diseases caused by inappropriate activation of the human complement system. However, marine streptomycetes producing anti-complement agents are still poorly explored. In this study, a marine-derived strain Streptomyces sp. DUT11 showing superior anti-complement activity was focused, and its genome sequence was analyzed. Gene clusters showing high similarities to that of tunicamycin and nonactin were identified, and their corresponding metabolites were also detected. Subsequently, tunicamycin I, V, and VII were isolated from Streptomyces sp. DUT11. Anti-complement assay showed that tunicamycin I, V, VII inhibited complement activation through the classic pathway, whereas no anti-complement activity of nonactin was detected. This is the first time that tunicamycins are reported to have such activity. In addition, genome analysis indicates that Streptomyces sp. DUT11 has the potential to produce novel lassopeptides and lantibiotics. These results suggest that marine Streptomyces are rich sources of anti-complement agents for drug discovery.

  10. The Surface-Exposed Protein SntA Contributes to Complement Evasion in Zoonotic Streptococcus suis.

    Science.gov (United States)

    Deng, Simin; Xu, Tong; Fang, Qiong; Yu, Lei; Zhu, Jiaqi; Chen, Long; Liu, Jiahui; Zhou, Rui

    2018-01-01

    Streptococcus suis is an emerging zoonotic pathogen causing streptococcal toxic shock like syndrome (STSLS), meningitis, septicemia, and even sudden death in human and pigs. Serious septicemia indicates this bacterium can evade the host complement surveillance. In our previous study, a functionally unknown protein SntA of S. suis has been identified as a heme-binding protein, and contributes to virulence in pigs. SntA can interact with the host antioxidant protein AOP2 and consequently inhibit its antioxidant activity. In the present study, SntA is identified as a cell wall anchored protein that functions as an important player in S. suis complement evasion. The C3 deposition and membrane attack complex (MAC) formation on the surface of sntA -deleted mutant strain Δ sntA are demonstrated to be significantly higher than the parental strain SC-19 and the complementary strain CΔ sntA . The abilities of anti-phagocytosis, survival in blood, and in vivo colonization of Δ sntA are obviously reduced. SntA can interact with C1q and inhibit hemolytic activity via the classical pathway. Complement activation assays reveal that SntA can also directly activate classical and lectin pathways, resulting in complement consumption. These two complement evasion strategies may be crucial for the pathogenesis of this zoonotic pathogen. Concerning that SntA is a bifunctional 2',3'-cyclic nucleotide 2'-phosphodiesterase/3'-nucleotidase in many species of Gram-positive bacteria, these complement evasion strategies may have common biological significance.

  11. The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

    Directory of Open Access Journals (Sweden)

    Marcell Cserhalmi

    2017-09-01

    Full Text Available Factor H-related (FHR proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH. While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3, and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

  12. DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

    Science.gov (United States)

    SanGiovanni, John Paul; Chen, Jing; Sapieha, Przemyslaw; Aderman, Christopher M; Stahl, Andreas; Clemons, Traci E; Chew, Emily Y; Smith, Lois E H

    2013-01-01

    Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and use of peroxisome proliferator activator receptor (PPAR)-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG) co-activator 1 alpha (PPARGC1A), a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR) transcription complex, may influence neovascularization (NV) in age-related macular degeneration (AMD). We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A. A DNA coding variant (rs3736265) and a 3'UTR-resident regulatory variant (rs3774923) in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs). SNP-SNP interactions existed for NV AMD (Pcomplement factor B (CFB, rs512559). PPARGC1A influences activation of the AMD-associated complement component 3 (C3) promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P ≤ 0.003) of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033), a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678) showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P ≤ 0.003). C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice - these animals also showed 70% reduction in retinal NV (P

  13. Trichinella spiralis Calreticulin Binds Human Complement C1q As an Immune Evasion Strategy.

    Science.gov (United States)

    Zhao, Limei; Shao, Shuai; Chen, Yi; Sun, Ximeng; Sun, Ran; Huang, Jingjing; Zhan, Bin; Zhu, Xinping

    2017-01-01

    As a multicellular parasitic nematode, Trichinella spiralis regulates host immune responses by producing a variety of immunomodulatory molecules to escape from host immune attack, but the mechanisms underlying the immune evasion are not well understood. Here, we identified that T. spiralis calreticulin ( Ts -CRT), a Ca 2+ -binding protein, facilitated T. spiralis immune evasion by interacting with the first component of human classical complement pathway, C1q. In the present study, Ts -CRT was found to be expressed on the surface of different developmental stages of T. spiralis as well as in the secreted products of adult and muscle larval worms. Functional analysis identified that Ts -CRT was able to bind to human C1q, resulting in the inhibition of C1q-initiated complement classical activation pathway reflected by reduced C4/C3 generation and C1q-dependent lysis of antibody-sensitized sheep erythrocytes. Moreover, recombinant Ts -CRT (r Ts -CRT) binding to C1q suppressed C1q-induced THP-1-derived macrophages chemotaxis and reduced monocyte-macrophages release of reactive oxygen intermediates (ROIs). Blocking Ts -CRT on the surface of newborn larvae (NBL) of T. spiralis with anti- Ts -CRT antibody increased the C1q-mediated adherence of monocyte-macrophages to larvae and impaired larval infectivity. All of these results suggest that T. spiralis -expressed Ts -CRT plays crucial roles in T. spiralis immune evasion and survival in host mostly by directly binding to host complement C1q, which not only reduces C1q-mediated activation of classical complement pathway but also inhibits the C1q-induced non-complement activation of macrophages.

  14. Complement System in the Pathogenesis of Benign Lymphoepithelial Lesions of the Lacrimal Gland.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available We aimed to examine the potential involvement of local complement system gene expression in the pathogenesis of benign lymphoepithelial lesions (BLEL of the lacrimal gland.We collected data from 9 consecutive pathologically confirmed patients with BLEL of the lacrimal gland and 9 cases with orbital cavernous hemangioma as a control group, and adopted whole genome microarray to screen complement system-related differential genes, followed by RT-PCR verification and in-depth enrichment analysis (Gene Ontology analysis of the gene sets.The expression of 14 complement system-related genes in the pathologic tissue, including C2, C3, ITGB2, CR2, C1QB, CR1, ITGAX, CFP, C1QA, C4B|C4A, FANCA, C1QC, C3AR1 and CFHR4, were significantly upregulated while 7 other complement system-related genes, C5, CFI, CFHR1|CFH, CFH, CD55, CR1L and CFD were significantly downregulated in the lacrimal glands of BLEL patients. The microarray results were consistent with RT-PCR analysis results. Immunohistochemistry analysis of C3c and C1q complement component proteins in the resected tissue were positive in BLEL patients, while the control group had negative expression of these proteins. Gene ontology (GO analysis revealed that activation of the genes of complement system-mediated signaling pathways were the most enriched differential gene group in BLEL patients.Local expression of complement components is prominently abnormal in BLEL, and may well play a role in its pathogenesis.

  15. Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury.

    Science.gov (United States)

    Damman, Jeffrey; Daha, Mohamed R; van Son, Willem J; Leuvenink, Henri G; Ploeg, Rutger J; Seelen, Marc A

    2011-04-01

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen activated protein kinases (MAPKs) might be the key molecules linking both the complement and TLR pathways together. Complement and TLRs are important mediators of renal ischemia-reperfusion injury (IRI). Besides IRI, complement C3 can also be upregulated and activated in the kidney before transplantation as a direct result of brain death (BD) in the donor. This local upregulation and activation of complement in the donor kidney has been proven to be detrimental for renal allograft outcome. Also TLR4 and several of its major ligands are upregulated by donor BD compared to living donors. Important and in line with the observations above, kidney transplant recipients have a benefit when receiving a kidney from a TLR4 Asp299Gly/Thr399Ile genotypic donor. The role of complement and TLRs and crosstalk between these two innate immune systems in relation to renal injury during donor BD and ischemia-reperfusion are focus of this review. Future strategies to target complement and TLR activation in kidney transplantation are considered. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Proteomic Analysis Reveals the Deregulation of Inflammation-Related Proteins in Acupuncture-Treated Rats with Asthma Onset

    Directory of Open Access Journals (Sweden)

    Yu-Dong Xu

    2012-01-01

    Full Text Available Although the beneficial effects of acupuncture in asthma treatment have been well documented, little is known regarding the biological basis of this treatment. Changes in the lung proteome of acupuncture-treated rats with asthma onset were comparatively analyzed using a two-dimensional gel electrophoresis (2DE and mass-spectrometry- (MS- based proteomic approach. Acupuncture on specific acupuncture points appeared to improve respiratory function and reduce the total number of leukocytes and eosinophils in bronchoalveolar lavage fluid in OVA-induced asthma onset. Image analysis of 2DE gels revealed 32 differentially expressed acupuncture-specific protein spots in asthma onset; 30 of which were successfully identified as 28 unique proteins using LC-MS/MS. Bioinformatic analyses indicated that these altered proteins are most likely involved in inflammation-related biological functions, and the functional associations of these proteins result in an inflammation signaling pathway. Acupuncture regulates the pathway at different levels by regulating several key nodal proteins, including downregulating of proinflammatory proteins (e.g., S100A8, RAGE, and S100A11 and upregulating of anti-inflammatory proteins (e.g., CC10, ANXA5, and sRAGE. These deregulated inflammation-related proteins may mediate, at least in part, the antiasthmatic effect of acupuncture. Further functional investigation of these acupuncture-specific effector proteins could identify new drug candidates for the prophylaxis and treatment of asthma.

  17. Pricing behaviour of pharmacies after market deregulation for OTC drugs: the case of Germany.

    Science.gov (United States)

    Stargardt, Tom; Schreyögg, Jonas; Busse, Reinhard

    2007-11-01

    To examine the price reactions of German pharmacies to changes made to OTC drug regulations in 2004. Prior to these changes, regulations guaranteed identical prices in all German pharmacies. Two years after market deregulation, 256 pharmacies were surveyed to determine the retail prices of five selected OTC drugs. A probit regression model was used to identify factors that increased the likelihood of price changes. In addition, 409 pharmacy consumers were interviewed to gather information on their knowledge of the regulatory changes and to better explain consumer behaviour. Data was collected on a total of 1215 prices. Two years after deregulation, 23.1% of the participating pharmacies had modified the price of at least one of the five OTCs included in our study. However, in total, only 7.5% of the prices differed from their pre-deregulation level. The probit model showed that population density and the geographic concentration of pharmacies were significantly associated with price changes. Interestingly, the association with the geographic concentration of pharmacies was negative. The consumer survey revealed that 47.1% of those interviewed were aware of the deregulation. Our findings indicate that, two years after deregulation, very few pharmacies had made use of individual pricing strategies; price competition between pharmacies in Germany is thus taking place only a very small scale.

  18. The deregulation of electricity and gas markets. The great economic challenges

    International Nuclear Information System (INIS)

    Mirabel, Francois; Guerassimoff, Gilles

    2012-01-01

    As the process of deregulation of electricity and gas markets started in Europe ten years ago, this book aims at recalling and describing the consequences of this evolution, notably for companies which were in a monopoly situation for electricity and gas production, transport, retailing and selling, but also in terms of new entities to be created and of entities having to give up their specialty. The author first presents the economic characteristics of gas and electricity industries in terms of infrastructures and final services, scale, coordination and size of energy networks, of existence of strong externalities in networks, of commitment in public service missions. He describes the background and implementation of this deregulation. He analyses the strategies of companies and how energy markets are controlled: strategies to mitigate competition and to strengthen their market power, firm strategies and public policies, merging strategies, strategies of competition distortion. The last chapter addresses the various priority fields of deregulation: public service missions in a deregulated environment (issues of service continuity and of affordable prices), the environmental constraint in energy market organisation (limitation of CO 2 emissions, promotion of renewable energies, and reduction of energy consumption). In conclusion, the author discusses how to conciliate deregulation and sustainable development of energy

  19. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.

    NARCIS (Netherlands)

    Hillmen, P.; Young, N.S.; Schubert, J.; Brodsky, R.A.; Socie, G.; Muus, P.; Roth, A.; Szer, J.; Elebute, M.O.; Nakamura, R.; Browne, P.; Risitano, A.M.; Hill, A.; Schrezenmeier, H.; Fu, C.L.; Maciejewski, J; Rollins, S.A.; Mojcik, C.F.; Rother, R.P.; Luzzatto, L.

    2006-01-01

    BACKGROUND: We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: We conducted a double-blind, randomized,

  20. Does Host Complement Kill Borrelia burgdorferi within Ticks?

    OpenAIRE

    Rathinavelu, Sivaprakash; Broadwater, Anne; de Silva, Aravinda M.

    2003-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, inhabits the gut lumen of the tick vector. At this location the spirochete is exposed to host blood when a tick feeds. We report here on studies that were done with normal and complement-deficient (C3-knockout) mice to determine if the host complement system killed spirochetes within the vector. We found that spirochete numbers within feeding nymphs were not influenced by complement, most likely because host complement was inactivated within ...

  1. Human Properdin Opsonizes Nanoparticles and Triggers a Potent Pro-inflammatory Response by Macrophages without Involving Complement Activation

    Science.gov (United States)

    Kouser, Lubna; Paudyal, Basudev; Kaur, Anuvinder; Stenbeck, Gudrun; Jones, Lucy A.; Abozaid, Suhair M.; Stover, Cordula M.; Flahaut, Emmanuel; Sim, Robert B.; Kishore, Uday

    2018-01-01

    Development of nanoparticles as tissue-specific drug delivery platforms can be considerably influenced by the complement system because of their inherent pro-inflammatory and tumorigenic consequences. The complement activation pathways, and its recognition subcomponents, can modulate clearance of the nanoparticles and subsequent inflammatory response and thus alter the intended translational applications. Here, we report, for the first time, that human properdin, an upregulator of the complement alternative pathway, can opsonize functionalized carbon nanotubes (CNTs) via its thrombospondin type I repeat (TSR) 4 and 5. Binding of properdin and TSR4+5 is likely to involve charge pattern/polarity recognition of the CNT surface since both carboxymethyl cellulose-coated carbon nanotubes (CMC-CNT) and oxidized (Ox-CNT) bound these proteins well. Properdin enhanced the uptake of CMC-CNTs by a macrophage cell line, THP-1, mounting a robust pro-inflammatory immune response, as revealed by qRT-PCR, multiplex cytokine array, and NF-κB nuclear translocation analyses. Properdin can be locally synthesized by immune cells in an inflammatory microenvironment, and thus, its interaction with nanoparticles is of considerable importance. In addition, recombinant TSR4+5 coated on the CMC-CNTs inhibited complement consumption by CMC-CNTs, suggesting that nanoparticle decoration with TSR4+5, can be potentially used as a complement inhibitor in a number of pathological contexts arising due to exaggerated complement activation. PMID:29483907

  2. Effect of truck and rail economic deregulation on radioactive material transportation

    International Nuclear Information System (INIS)

    Allen, G.C. Jr.

    1984-01-01

    An evaluation of the effect of truck and rail economic deregulation on radioactive material transportation is presented in this document. The evaluation is based on expected market performance that would be consistent with fundamental economic theories. The issues of transport safety, commodity discrimination and rates are addressed. Relative to transport safety, deregulation should not have any significant impact. While deregulation should not change commodity acceptance and may lower rates for motor carriage, it may allow increased discrimination by rail carriers in addition to raising rates. Consequently, it is likely that the radioactive material transportation industry will continue to place greater reliance on the competitive motor carrier industry. Positive steps that shippers can take are to maintain credible options to ship by alternate modes, to address issues that result in the perceived need for special risk premiums, and to reduce the cost of handling truck shipments by improvements in technology or procedures. 28 references, 3 figures, 6 tables

  3. Natural gas retailing: writing the last chapter of natural gas deregulation

    International Nuclear Information System (INIS)

    Bjerkelund, T.

    1995-01-01

    Under the A greement on Natural Gas Markets and Prices of October 1985, the Canadian federal government agreed to deregulate the price of natural gas and to allow a competitive gas market to develop. Several beneficial changes that have occurred as a result of the deregulation were described, including the Industrial Gas Users Association's (IGUA) view on the marketing and sale of natural gas by local gas distributor's (LDC) and the sale within the LDC franchise. IGUA's support for the separation between LDC distribution and LDC sales and marketing activities as the last step in deregulation process, was explained. Several arguments for the opposing view were also discussed. Recommendations were made for effective separation of LDC distribution and LDC sales/marketing activities

  4. U.S. Banking Deregulation and Emerging Market Loans: Potential Links and Evidence, 1984~2005

    Directory of Open Access Journals (Sweden)

    Hyun Koo Cho

    2010-06-01

    Full Text Available How did the deregulation of U.S. bank activities affect the patterns of cross-border lending to emerging economies? Unlike bank lending from Europe or Japan, U.S. bank lending to emerging economies exhibited increasing volatility over time. Using U.S. cross-border bank exposure data, this study identifies a temporal association between important deregulation initiatives and the volatility of U.S. bank emerging market lending. This association is explained by the linkages between an important outcome of bank deregulation-earnings volatility from diversified bank activities-and the rising volatility. Together, it argues that U.S. banking deregulation had unanticipated effects of exacerbating the volatility of bank lending to emerging economies.

  5. Learning without experience: Understanding the strategic implications of deregulation and competition in the electricity industry

    Energy Technology Data Exchange (ETDEWEB)

    Lomi, A. [School of Economics, University of Bologna, Bologna (Italy); Larsen, E.R. [Dept. of Managements Systems and Information, City University Business School, London (United Kingdom)

    1998-11-01

    As deregulation of the electricity industry continues to gain momentum around the world, electricity companies face unprecedented challenges. Competitive complexity and intensity will increase substantially as deregulated companies find themselves competing in new industries, with new rules, against unfamiliar competitors - and without any history to learn from. We describe the different kinds of strategic issues that newly deregulated utility companies are facing, and the risks that strategic issues implicate. We identify a number of problems induced by experiential learning under conditions of competence-destroying change, and we illustrate ways in which companies can activate history-independent learning processes. We suggest that Micro worlds - a new generation of computer-based learning environments made possible by conceptual and technological progress in the fields of system dynamics and systems thinking - are particularly appropriate tools to accelerate and enhance organizational and managerial learning under conditions of increased competitive complexity. (au)

  6. A NEPOTISM AND CRONY IN A BUSINESS, CASE OF INDUSTRIAL DEREGULATION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Muhadjir Efendy

    2011-06-01

    Full Text Available An industrial deregulation is a government policy in developing a state’s economic infrastructure. If a country undergoes a process of powerful personalization, its interest is identical with a powerful interest. For an economic profit, the President’s relative and crony do a business and build directly unproductive seeking activities. This study aims to examine the relation of relative to crony in realizing an industrial deregulation in the 1980s and its impact on the Indonesian economy in a view of macroeconomic policy. It focuses on a problem of the industrial deregulation from 1983 to 1990 with economic growth by the indicator of contribution to GDP and labor force. The study used an expose facto approach. The data were the secondary sources: documents, textbooks and mass media. It used a qualitative-descriptive analysis.

  7. Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System.

    Science.gov (United States)

    Weinberger, Katherine; Collazo, Norberto; Aguillón, Juan Carlos; Molina, María Carmen; Rosas, Carlos; Peña, Jaime; Pizarro, Javier; Maldonado, Ismael; Cattan, Pedro E; Apt, Werner; Ferreira, Arturo

    2017-02-08

    Triatoma infestans is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1. In previous studies, we have detected CRT in salivary gland extracts from T. infestans We have called this molecule TiCRT. Given that the S domain is responsible for C1 binding, we have tested its role in the classical pathway of complement activation in vertebrate blood. We have cloned and characterized the complete nucleotide sequence of CRT from T. infestans , and expressed its S domain. As expected, this S domain binds to human C1 and, as a consequence, it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous insects to control a potential activation of complement proteins, present in the massive blood meal that they ingest, with deleterious consequences at least on the anterior digestive tract of these insects. © The American Society of Tropical Medicine and Hygiene.

  8. Optimal electricity price calculation model for retailers in a deregulated market

    Energy Technology Data Exchange (ETDEWEB)

    Yusta, J.M.; Dominguez-Navarro, J.A. [Zaragoza Univ., Dept. of Electrical Engineering, Zaragoza (Spain); Ramirez-Rosado, I.J. [La Rioja Univ., Dept. of Electrical Engineering, Logrono (Spain); Perez-Vidal, J.M. [McKinnon and Clarke, Energy Services Div., Zaragoza (Spain)

    2005-07-01

    The electricity retailing, a new business in deregulated electric power systems, needs the development of efficient tools to optimize its operation. This paper defines a technical-economic model of an electric energy service provider in the environment of the deregulated electricity market in Spain. This model results in an optimization problem, for calculating the optimal electric power and energy selling prices that maximize the economic profits obtained by the provider. This problem is applied to different cases, where the impact on the profits of several factors, such as the price strategy, the discount on tariffs and the elasticity of customer demand functions, is studied. (Author)

  9. Optimal electricity price calculation model for retailers in a deregulated market

    International Nuclear Information System (INIS)

    Yusta, J.M.; Dominguez-Navarro, J.A.; Ramirez-Rosado, I.J.; Perez-Vidal, J.M.

    2005-01-01

    The electricity retailing, a new business in deregulated electric power systems, needs the development of efficient tools to optimize its operation. This paper defines a technical-economic model of an electric energy service provider in the environment of the deregulated electricity market in Spain. This model results in an optimization problem, for calculating the optimal electric power and energy selling prices that maximize the economic profits obtained by the provider. This problem is applied to different cases, where the impact on the profits of several factors, such as the price strategy, the discount on tariffs and the elasticity of customer demand functions, is studied. (Author)

  10. Deregulation and growth in China's energy sector: a review of recent development

    International Nuclear Information System (INIS)

    Wu, Yanrui.

    2003-01-01

    Dramatic changes have taken place in China's energy sector over the past decade. These changes have important implications for energy consumption, trade, production and regulatory policies in China and beyond. The objective of this paper is to review some of the key issues associated with deregulation and growth in China's energy sector. Specifically, the paper presents a survey of recent reforms in this sector; it also analyses the impact of deregulation on energy policy, ownership, foreign investment and trade, and sheds some lights on the sources of growth in China's energy sector

  11. Assessment for feasibility and pricing of wheeling transactions under deregulated environment of power industry

    International Nuclear Information System (INIS)

    Yog Raj Sood; Narayana Prasad Padhy; Hari Om Gupta

    2004-01-01

    Many transactions of electrical power are expected to take place due to deregulation of electrical power industry. It is important for independent power producers, independent system operator and bulk power consumers (load centers) to know and select the least cost transaction among all the feasible transactions. In this paper, selection of best possible wheeling transaction in a deregulated power system has been determined based on available transfer capability and short run marginal cost. The proposed algorithm has been tested and analyzed for IEEE-30 bus test system and hence applied to South African power industry, the results so obtained are found to be of very much practical use. (author)

  12. Impacts of Contingency Reserve on Nodal Price and Nodal Reliability Risk in Deregulated Power Systems

    DEFF Research Database (Denmark)

    Zhao, Qian; Wang, Peng; Goel, Lalit

    2013-01-01

    The deregulation of power systems allows customers to participate in power market operation. In deregulated power systems, nodal price and nodal reliability are adopted to represent locational operation cost and reliability performance. Since contingency reserve (CR) plays an important role...... in reliable operation, the CR commitment should be considered in operational reliability analysis. In this paper, a CR model based on customer reliability requirements has been formulated and integrated into power market settlement. A two-step market clearing process has been proposed to determine generation...

  13. Deregulation potentials in the Federal Republic of Germany. Deregulierungspotentiale in der Bundesrepublik

    Energy Technology Data Exchange (ETDEWEB)

    Soltwedel, R; Busch, A; Gross, A; Laaser, C F

    1986-01-01

    In December 1984 the Federal Minister of Economics commissioned the Institute of World Trade and Industry to work out an expertise on 'deregulation potentials in the Federal Republic of Germany'. The study gives access to major parts of the expertise. Analyses focus on regulations for different self-supporting occupations, retail trade, the finance markets, the communication sector, the supply industry, and the transportation sector. An examination of the grounds the regulations were based on is followed by a discussion of the pros and cons of a deregulation. The statements and arguments take into account experiences gained abroad.

  14. Changes in competitive strategies due to deregulation and privatization in the petroleum industry: a comparative study

    International Nuclear Information System (INIS)

    Teixeira Carneiro, J.M.; Moutinho Dos Santos, E.

    1999-01-01

    This article is part of a series of four dedicated to the study of the global oil competition game through the analytical framework proposed by Michael Porter, from the University of Harvard. By means of a questionnaire answered by top executives in ten oil companies, the authors investigate the changes in the competitive strategy of these companies in the downstream side of the oil business due to deregulation and privatization. The paper starts by establishing the relationship between Porter's generic competitive strategies and specific competitive methods. Then, it describes how companies have changes their competitive methods after privatization and major deregulation. Changes in the industry structure are also analyzed. (authors)

  15. The deregulation effects of Finnish electricity markets on district heating prices

    International Nuclear Information System (INIS)

    Linden, Mikael; Peltola-Ojala, Paeivi

    2010-01-01

    This paper investigates an empirical econometric panel data model in order to test deregulation and regional market structure effects on district heating prices in Finland for period 1996-2002. The data was collected from 76 district heating firms throughout Finland. Special emphasis is placed on the modeling of policy-induced competition, which began in year 1999, regional based fuel selection, local market structures, and distribution network sharing effects. The results imply that the local structures of energy production and sales have an important role to play in the formation of market prices and that the price lowering effects of energy market deregulation are permanent. (author)

  16. Electric power industry deregulation in the United States: impacts on U.S. and Canadian markets

    Energy Technology Data Exchange (ETDEWEB)

    Hall, G.R. [Putnam, Hayes and Bartlett, Inc., Cambridge, MA (United States)

    1996-10-01

    An overview of the restructuring and deregulation of the United States electric power industry and the implications for the North American natural gas industry was presented. Electric power restructuring and its effect on wholesale and retail competition was discussed. It was suggested that although in the short term electric power deregulation impacts negatively on the natural gas industry, the long term impacts are favourable. The short term impact on the natural gas industry will mean increased competition and downward pressure on gas prices. In contrast, the long term impact could mean increased reliance on gas for electric power generation and convergence of the electric power and natural gas industries.

  17. Does Deregulation of Quality Standards in Telecomunications Improve Social Welfare? A Methodological Note Does Deregulation of Quality Standards in Telecomunications Improve Social Welfare? A Methodological Note

    OpenAIRE

    Felipe Morandé

    1990-01-01

    Does Deregulation of Quality Standards in Telecomunications Improve Social Welfare? A Methodological Note One of the main reasons behind the bit difference observed in the per capita number of telephones between develope and developing countries is the high capital cost -a scarce resource in LDC's- of expanding telecommunications infrastructure. A reasonable question to raise in this context is the extent to which that high capital cost of investment could be diminished if international quali...

  18. Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion.

    Science.gov (United States)

    Hovingh, Elise S; van den Broek, Bryan; Jongerius, Ilse

    2016-01-01

    The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

  19. Masturbation and Partnered Sex: Substitutes or Complements?

    Science.gov (United States)

    Regnerus, Mark; Price, Joseph; Gordon, David

    2017-10-01

    Drawing upon a large, recent probability sample of American adults ages 18-60 (7648 men and 8090 women), we explored the association between sexual frequency and masturbation, evaluating the evidence for whether masturbation compensates for unavailable sex, complements (or augments) existing paired sexual activity, or bears little association with it. We found evidence supporting a compensatory relationship between masturbation and sexual frequency for men, and a complementary one among women, but each association was both modest and contingent on how content participants were with their self-reported frequency of sex. Among men and women, both partnered status and their sexual contentment were more obvious predictors of masturbation than was recent frequency of sex. We conclude that both hypotheses as commonly evaluated suffer from failing to account for the pivotal role of subjective sexual contentment in predicting masturbation.

  20. Endogenous Natural Complement Inhibitor Regulates Cardiac Development

    DEFF Research Database (Denmark)

    Mortensen, Simon A; Skov, Louise L; Kjaer-Sorensen, Kasper

    2017-01-01

    mechanisms during fetal development and adult homeostasis. In this article, we describe the function of an endogenous complement inhibitor, mannan-binding lectin (MBL)-associated protein (MAp)44, in regulating the composition of a serine protease-pattern recognition receptor complex, MBL-associated serine...... of MAp44 caused impaired cardiogenesis, lowered heart rate, and decreased cardiac output. These defects were associated with aberrant neural crest cell behavior. We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and knockdown of endogenous MAp44 expression could...... be rescued by overexpression of wild-type MAp44. Our observations provide evidence that immune molecules are centrally involved in the orchestration of cardiac tissue development....